MF研究者総覧

研究者データベース

詳細
加瀬　諭(カセ　サトル)
北海道大学病院　脳・神経・感覚器科
講師
researchmap個人ページ
Last Updated :2023/11/02

基本情報

所属

  • 北海道大学病院　脳・神経・感覚器科

職名

  • 講師

学位

  • 医学博士（鳥取大学）

ホームページURL

J-Global ID

研究キーワード

  • 眼病理学   alpha-crystallin   血管新生   VEGF   alphaB-crystallin   糖尿病網膜症   眼窩腫瘍   白血球接着分子   

研究分野

  • ライフサイエンス / 眼科学

担当教育組織

職歴

  • 2015年 北海道大学 医学(系)研究科(研究院)

学歴

  • 2015年04月 - 現在   北海道大学   大学院医学研究院眼科学教室
  • 2012年04月 - 2015年03月   手稲渓仁会病院眼科   主任医長
  • 2010年04月 - 2012年03月   北海道大学眼科学教室医員
  • 2007年04月 - 2010年03月   独立行政法人日本学術振興会   特別研究員 PD-1
  • 2007年04月 - 2008年09月   南カリフォルニア大学ドヒニー眼研究所リサーチフェロー
  • 2006年04月 - 2007年03月   札幌社会保険総合病院眼科
  • 2003年04月 - 2006年03月   北海道大学医学部附属病院眼科
  • 1999年04月 - 2003年03月   鳥取大学医学部大学院器官病理学教室

研究活動情報

論文

  • Taku Yamamoto, Satoru Kase, Akihiro Shinkai, Miyuki Murata, Kasumi Kikuchi, Di Wu, Yasushi Kageyama, Masami Shinohara, Tomohiko Sasase, Susumu Ishida
    Investigative ophthalmology & visual science 64 10 20 - 20 2023年07月03日 
    PURPOSE: Chronic inflammation plays a pivotal role in the pathology of proliferative diabetic retinopathy (PDR), in which biological alterations of retinal glial cells are one of the key elements. The phosphorylation of αB-crystallin/CRYAB modulates its molecular dynamics and chaperone activity, and attenuates αB-crystallin secretion via exosomes. In this study, we investigated the effect of phosphorylated αB-crystallin in retinal Müller cells on diabetic mimicking conditions, including interleukin (IL)-1β stimuli. METHODS: Human retinal Müller cells (MIO-M1) were used to examine gene and protein expressions with real-time quantitative PCR, enzyme linked immunosorbent assay (ELISA), and immunoblot analyses. Cell apoptosis was assessed by Caspase-3/7 assay and TdT-mediated dUTP nick-end labeling staining. Retinal tissues isolated from the Spontaneously Diabetic Torii (SDT) fatty rat, a type 2 diabetic animal model with obesity, and fibrovascular membranes from patients with PDR were examined by double-staining immunofluorescence. RESULTS: CRYAB mRNA was downregulated in MIO-M1 cells with the addition of 10 ng/mL IL-1β; however, intracellular αB-crystallin protein levels were maintained. The αB-crystallin serine 59 (Ser59) residue was phosphorylated with IL-1β application in MIO-M1 cells. Cell apoptosis in MIO-M1 cells was induced by CRYAB knockdown. Immunoreactivity for Ser59-phosphorylated αB-crystallin and glial fibrillary acidic protein was colocalized in glial cells of SDT fatty rats and fibrovascular membranes. CONCLUSIONS: The Ser59 phosphorylation of αB-crystallin was modulated by IL-1β in Müller cells under diabetic mimicking inflammatory conditions, suggesting that αB-crystallin contributes to the pathogenesis of PDR through an anti-apoptotic effect.
  • Kanae Fukutsu, Michiyuki Saito, Kousuke Noda, Miyuki Murata, Satoru Kase, Ryosuke Shiba, Naoki Isogai, Yoshikazu Asano, Nagisa Hanawa, Mitsuru Dohke, Manabu Kase, Susumu Ishida
    Current eye research 47 11 1534 - 1537 2022年11月 
    PURPOSE: Retinal vessels reflect alterations related to hypertension and arteriosclerosis in the physical status. Previously, we had reported a deep-learning algorithm for automatically detecting retinal vessels and measuring the total retinal vascular area in fundus photographs (VAFP). Herein, we investigated the relationship between VAFP and brachial-ankle pulse wave velocity (baPWV), which is the gold standard for arterial stiffness assessment in clinical practice. METHODS: Retinal photographs (n = 696) obtained from 372 individuals who visited the Keijinkai Maruyama Clinic for regular health checkups were used to analyze VAFP. Additionally, the baPWV was measured for each patient. Automatic retinal-vessel segmentation was performed using our deep-learning algorithm, and the total arteriolar area (AA) and total venular area (VA) were measured. Correlations between baPWV and several parameters, including AA and VA, were assessed. RESULTS: The baPWV was negatively correlated with AA (R = -0.40, n = 696, P < 2.2e-16) and VA (R = -0.36, n = 696, P < 2.2e-16). Independent variables (AA, sex, age, and systolic blood pressure) selected using the stepwise method showed a significant correlation with baPWV. The estimated baPWV, calculated using a regression equation with variables including AA, showed a better correlation with the measured baPWV (R = 0.70, n = 696, P < 2.2e-16) than the estimated value without AA (R = 0.68, n = 696, P < 2.2e-16). CONCLUSIONS: AA and VA were significantly correlated with baPWV. Moreover, baPWV estimated using AA correlated well with the actual baPWV. VAFP may serve as an alternative biomarker for evaluating systemic arterial stiffness.
  • Mizuho Mitamura, Satoru Kase, Yasuo Suzuki, Takatoshi Sakaguchi, Yuka Suimon, Toshiya Sinohara, A I Shimizu, Yoshihiro Matsuno, Hajime Sakai, Manabu Kase, Susumu Ishida
    European journal of ophthalmology 11206721221127053 - 11206721221127053 2022年09月16日 
    PURPOSE: The aim of this study was to evaluate the clinicopathological features and flow cytometry (FCM) of tumor tissues in ocular adnexal diffuse large B-cell lymphoma (DLBCL). METHODS: This retrospective, multicenter case study was designed to evaluate the clinical and immunohistochemical features of tumors. DLBCL was diagnosed based on histopathology, immunoglobulin (Ig) heavy chain gene rearrangement, and FCM in all surgically removed periocular tumor tissues. This study involved assessing percentages (%) of B-cell/T-cell markers, a natural killer cell marker, and cell-surface Ig kappa/lambda (κ/λ) expression measured by FCM analysis in tumor tissues. RESULTS: Eleven DLBCL patients (4 men and 7 women) with 11 tumors were enrolled in this study. The median age at the time of initial presentation was 73 years. The tumor cells were immunohistochemically positive for cluster of differentiation (CD) 20, while CD5 was negative in all 8 cases tested. At the time of ophthalmic diagnosis, two cases already showed systemic dissemination of DLBCL throughout the body. FCM of tumor tissues detected a high percentage of B-cell markers including CD19 and CD20 in all 11 tumors. One case with high CD10 levels in FCM was histologic transformation from follicular lymphoma. One case with a relatively low CD20 population involved a history of systemic treatments including intravenous rituximab. CONCLUSION: Although caution should be exercised when interpreting the data, FCM is useful for not only supportive diagnosis complementary to immunohistochemistry, but also facilitates a better understanding of immunopathology including histologic transformation of follicular lymphoma to DLBCL in the ocular adnexa.
  • Miyuki Murata, Kousuke Noda, Satoru Kase, Keitaro Hase, Di Wu, Ryo Ando, Susumu Ishida
    The Journal of biological chemistry 298 9 102378 - 102378 2022年09月 
    Placental growth factor (PlGF) belongs to the vascular endothelial growth factor (VEGF) family of proteins that participate in angiogenesis and vasculogenesis. Anti-VEGF therapy has become the standard treatment for ocular angiogenic disorders in ophthalmological practice. However, there is emerging evidence that anti-VEGF treatment may increase the risk of atrophy of the retinal pigment epithelium (RPE), which is important for the homeostasis of retinal tissue. Whereas the cytoprotective role of VEGF family molecules, particularly that of VEGF A (VEGFA) through its receptor VEGF receptor-2 (VEGFR-2), has been recognized, the physiological role of PlGF in the retina is still unknown. In this study, we explored the role of PlGF in the RPE using PlGF-knockdown RPE cells generated by retrovirus-based PlGF-shRNA transduction. We show that VEGFA reduced apoptosis induced by serum starvation in RPE cells, whereas the antiapoptotic effect of VEGFA was abrogated by VEGFR-2 knockdown. Furthermore, PlGF knockdown increased serum starvation-induced cell apoptosis and unexpectedly reduced the protein level of VEGFR-2 in the RPE. The antiapoptotic effect of VEGFA was also diminished in PlGF-knockdown RPE cells. In addition, we found that glycogen synthase kinase 3 activity was involved in proteasomal degradation of VEGFR-2 in RPE cells and inactivated by PlGF via AKT phosphorylation. Overall, the present data demonstrate that PlGF is crucial for RPE cell viability and that PlGF supports VEGFA/VEGFR-2 signaling by stabilizing the VEGFR-2 protein levels through glycogen synthase kinase 3 inactivation.
  • Taku Yamamoto, Satoru Kase, Miyuki Murata, Susumu Ishida
    Biomedical reports 16 4 28 - 28 2022年04月 
    αB-crystallin, one of the small heat shock proteins, which is also known as HSPB5, has cytoprotective effects under inflammatory conditions. Advanced glycation end-products (AGE) are produced through non-enzymatic glycation under conditions of hyperglycemia and they contribute to angiogenesis and inflammation. The aim of this study was to examine the levels of serum αB-crystallin and AGE concentrations in blood samples collected from proliferative diabetic retinopathy (PDR) patients. Blood samples were collected from seven diabetic patients with PDR and eight patients without diabetes mellitus who underwent vitrectomy due to PDR and idiopathic macular diseases, respectively, in a single center. The levels of serum αB-crystallin and AGE were measured by ELISA and correlations were assessed statistically. The serum levels (mean ± SEM) of AGE were significantly higher in PDR patients (28.41±0.46 µg/ml) than in patients with non-diabetic macular diseases (25.76±0.60 µg/ml; P=0.015), whereas there was no significant difference in serum αB-crystallin levels. There was one patient with an extremely high level of αB-crystallin, who was treated with systemic corticosteroid due to chronic autoimmune inflammatory diseases. The current prospective study showed that serum AGE levels were significantly higher in PDR patients; however, no correlations between serum AGE and αB-crystallin levels were identified.
  • D I Wu, Satoru Kase, Y E Liu, Atsuhiro Kanda, Miyuki Murata, Susumu Ishida
    In vivo (Athens, Greece) 36 1 132 - 139 2022年 
    BACKGROUND/AIM: AlphaB-crystallin plays a pivotal role in many diseases. However, the involvement of alphaB-crystallin in retinal pigment epithelial (RPE) cells with diabetes stimuli remains unknown. The aim of this study is to examine the alterations of RPE cells and alphaB-crystallin expression in diabetic models in vivo and in vitro. MATERIALS AND METHODS: Diabetic conditions in mice were induced by streptozotocin (STZ). The thickness of the RPE/choroid complex was measured by optical coherence tomography (OCT). Periodic acid-Schiff (PAS) staining was used to investigate the choriocapillaris in histological sections of murine eyeballs and oxidative stress was evaluated using immunofluorescence with anti-4-hydroxynonenal (HNE) antibody. AlphaB-crystallin expression was examined in the RPE/choroid complex using ELISA. Real-Time PCR was performed to evaluate the alphaB-crystallin expression in cultured human RPE cells with high glucose or following advanced glycation end-products (AGE) stimulation. RESULTS: In diabetic mice, OCT-based RPE/choroidal layers were thickened 2 months after STZ stimulation, where PAS-positive dilated choriocapillaris was noted. Immunoreactivity of 4-HNE was strongly observed in the RPE layer, from which a significant number of RPE cells was lost. Meanwhile, alphaB-crystallin expression in 2-month STZ mice was significantly lower compared to controls. In accordance with these results, in vitro data showed that the alphaB-crystallin expression was also significantly lower in RPE cells with high glucose or following AGE stimulation compared to untreated cells. CONCLUSION: In both types of diabetic models the expression of alphaB-crystallin was found to be downregulated in RPE cells and was associated with increased levels of oxidative stress.
  • Taku Yamamoto, Atsuhiro Kanda, Satoru Kase, Susumu Ishida
    Investigative ophthalmology & visual science 62 2 22 - 22 2021年02月01日 
    Purpose: Galectin-1/LGALS1, a β-galactoside-binding protein, contributes to angiogenesis and fibrosis in various ocular diseases. Hypoxia-dependent and -independent pathways upregulate galectin-1/LGALS1 expression in Müller glial cells. Here, we present novel findings on the galectin-1/LGALS1 regulatory system in human retinal pigment epithelium (RPE) cells, the major cellular participant in the pathogenesis of neovascular age-related macular degeneration (nAMD). Methods: Human RPE cells were used to evaluate changes in gene and protein expression with real-time quantitative PCR and immunoblot analyses, respectively. The promoter and enhancer regions of LGALS1 were analyzed by reporter assay and chromatin immunoprecipitation. Immunofluorescence analysis of nAMD patient specimens was used to confirm the in vitro findings. Results: Hypoxia induced galectin-1/LGALS1 expression via binding of hypoxia-inducible factor 1α (HIF-1α) to hypoxia-responsive elements in the LGALS1 promoter region. Blockade of vascular endothelial growth factor receptor 1 (VEGFR1) partially decreased hypoxia-induced galectin-1/LGALS1 expression. Among several VEGFR1 ligands induced by hypoxia, placental growth factor (PlGF)/PGF alone upregulated galectin-1/LGALS1 expression via phosphorylation of activator protein 1 (AP-1) subunits following AKT and p38 mitogen-activated protein kinase (MAPK) activation. An AP-1 site in the LGALS1 enhancer region was required for PlGF-induced galectin-1/LGALS1 expression in RPE cells. PlGF application upregulated PGF expression via extracellular signal-regulated kinase 1 and 2, AKT, and p38 MAPK pathways. nAMD patient specimens demonstrated co-localization of galectin-1 with HIF-1α, PlGF, and VEGFR1 in RPE cells. Conclusions: Our present findings implicate the significance of hypoxia as a key inducer of galectin-1/LGALS1 in RPE cells and the autoinduction of hypoxia-induced PlGF as a vicious cycle amplifying the pathogenesis of nAMD.
  • Kanae Fukutsu, Michiyuki Saito, Kousuke Noda, Miyuki Murata, Satoru Kase, Ryosuke Shiba, Naoki Isogai, Yoshikazu Asano, Nagisa Hanawa, Mitsuru Dohke, Manabu Kase, Susumu Ishida
    Ophthalmology Science 100004 - 100004 2021年02月
  • Akihiro Shinkai, Wataru Saito, Yuki Hashimoto, Michiyuki Saito, Satoru Kase, Kousuke Noda, Susumu Ishida
    Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 2020年11月04日 
    PURPOSE: This study aimed to demonstrate the clinical course of Japanese patients with macular telangiectasia type 2 (MacTel-2). METHODS: This retrospective observational case series included 16 eyes of 8 Japanese patients (3 men and 5 women) with MacTel-2. The mean age and follow-up duration was 66.9 years and 42.8 months, respectively. Differences in best-corrected visual acuity (BCVA), funduscopic macular findings, central macular thickness (CMT), and the length of macular ellipsoid zone (EZ) loss were compared between the initial/baseline and final visits. Optical coherence tomographic changes in CMT by ≥ 20% and in EZ loss by ≥ 20% or ≥ 100 μm were defined as improved or worsened. RESULTS: Numerical changes in BCVA and EZ loss during follow-up were not statistically significant. However, the mean CMT at baseline, which was lower than that of healthy control eyes (P < 0.001), significantly increased during follow-up (P = 0.041). A certain proportion of eyes showed improvement in several parameters: funduscopic findings (both parafoveal retinal graying and foveal retinal pigment epithelium depigmentation) in 29% of eyes, CMT in 21% of eyes, and EZ loss in 43% of eyes. CONCLUSIONS: The non-negligible proportion of eyes with improved parameters, marked especially by macular EZ loss, suggests that Japanese patients with MacTel-2 have milder clinical features than Caucasian patients reported in the literature.
  • 硝子体内鉄片異物を経前房的に摘出した3例
    長谷川 綾華, 清水 啓史, 柴田 有紀子, 品川 真有子, 齋藤 理幸, 加瀬 諭, 野田 航介, 石田 晋
    眼科臨床紀要 13 11 739 - 739 眼科臨床紀要会 2020年11月
  • 脈絡膜瘢痕病巣を生じた急性特発性黄斑症の1例
    大田 翔一郎, 齋藤 理幸, 鈴木 智浩, 清水 啓史, 橋本 勇希, 加瀬 諭, 野田 航介, 石田 晋
    眼科臨床紀要 13 11 743 - 743 眼科臨床紀要会 2020年11月
  • Pachychoroid関連疾患と鑑別を要したchoroidal macrovesselの1例
    片岡 慶次, 加瀬 諭, 長谷川 綾華, 柴田 有紀子, 品川 真有子, 清水 啓史, 齋藤 理幸, 野田 航介, 石田 晋
    眼科臨床紀要 13 11 749 - 749 眼科臨床紀要会 2020年11月
  • ポリープ状脈絡膜血管症に対するphotodynamic therapyトリプル療法におけるpachychoroidの有無での治療成績の比較
    柴田 有紀子, 安藤 亮, 野田 航介, 廣岡 季里子, 長谷川 綾華, 品川 真有子, 清水 啓史, 齋藤 理幸, 加瀬 諭, 齋藤 航, 石田 晋
    眼科臨床紀要 13 11 752 - 752 眼科臨床紀要会 2020年11月
  • 機械学習によって自動算出された網膜動静脈面積と血圧脈波の関係
    福津 佳苗, 齋藤 理幸, 野田 航介, 村田 美幸, 加瀬 諭, 柴 涼介, 磯貝 直己, 道家 充, 石田 晋
    眼科臨床紀要 13 10 683 - 684 眼科臨床紀要会 2020年10月
  • 抗carbonic anhydrase II抗体陽性自己免疫性網膜症の臨床像
    安藤 亮, 齋藤 航, 平形 寿彬, 藤波 芳, 角田 和繁, 加瀬 諭, 野田 航介, 神田 敦宏, 石田 晋
    眼科臨床紀要 13 10 684 - 684 眼科臨床紀要会 2020年10月
  • Hiroaki Endo, Satoru Kase, Michiyuki Saito, Masahiko Yokoi, Mitsuo Takahashi, Susumu Ishida, Manabu Kase
    American journal of ophthalmology 218 68 - 77 2020年10月 [査読有り][通常論文]
     
    PURPOSE: To evaluate the relationship between diabetic eyes without diabetic retinopathy and healthy eyes in subfoveal choroidal thickness. DESIGN: Systematic review and meta-analysis. METHODS: An independent retrospective or prospective clinical study comparing diabetic eyes without diabetic retinopathy and healthy control eyes in the subfoveal choroidal thickness was selected. This study compiled data from publications in PubMed and Web of Science between January 1, 2008, and November 15, 2019. Heterogeneity was statistically quantified by I2 statistics, and meta-analysis was performed using a random-effects model. RESULTS: Seventeen related studies were identified, including a total of 4,213 eyes, which consisted of 1,197 diabetic eyes without diabetic retinopathy and 3,016 healthy eyes. Meta-analysis clearly showed that the subfoveal choroidal thickness of diabetic eyes without retinopathy was significantly thinner than that of healthy control eyes (weighted mean difference = -14.34 μm; 95% confidence interval: -24.37 to -4.32 μm; P < .005). Similar results were obtained in sub-analysis based on the adjustment of the axial length. CONCLUSIONS: This study suggests that the subfoveal choroidal thickness was thin in diabetic eyes without retinopathy compared to healthy eyes. Subfoveal choroidal thickness might be an important parameter for the development of diabetic retinopathy in diabetic eyes without retinopathy.
  • 機械学習によるFA画像からの網膜静脈分枝閉塞症の視力予後の推量
    品川 真有子, 齋藤 理幸, 高橋 光生, 伊藤 有希, 遠藤 弘毅, 加瀬 諭, 野田 航介, 石田 晋
    眼科臨床紀要 13 9 638 - 638 眼科臨床紀要会 2020年09月
  • Yuka Suimon, Satoru Kase, Shuhei Shimoyama, Susumu Ishida
    Ophthalmic plastic and reconstructive surgery 2020年07月13日 [査読有り][通常論文]
     
    IgG4-related disease (IgG4-RD) is a fibro-inflammatory condition characterized by lymphoplasmacytic infiltrates rich in IgG4-positive plasma cells, often with elevated serum IgG4. Multiple organs may be affected. Coronary arteritis may be one form of fatal involvement in IgG4-RD. IgG4-RD can manifest as periocular lesions, called IgG4-related ophthalmic disease (IgG4-ROD). Here, the authors describe a patient with asymptomatic coronary arteritis detected after the diagnosis of IgG4-ROD. A 58-year-old male complained of eyelid swelling and diplopia without systemic symptoms. Swelling of bilateral lacrimal glands and infraorbital nerves, high serum IgG4 levels, and histopathology of lacrimal gland tissue fulfilled diagnostic criteria for IgG4-ROD. After diagnosis, systemic and coronary CT showed coronary lesions and coronary artery stenosis. After prednisolone at 40 mg/day was administered, swelling of the lacrimal glands, diplopia, and coronary lesions improved. This case emphasizes the importance of systemic screening, even if initial symptoms are solely associated with periocular regions.
  • Mizuho Mitamura, Satoru Kase, Susumu Ishida
    BMC ophthalmology 20 1 248 - 248 2020年06月22日 [査読有り][通常論文]
     
    BACKGROUND: Sclerochoroidal calcification (SCC), a rare condition found in elderly people, is idiopathic or occasionally secondary to disorders affecting calcium metabolism. Findings of multimodal imaging including choroidal circulation are, however, largely unknown. We present a patient of SCC with systemic background, who underwent multimodal imaging evaluations. CASE PRESENTATION: A 70-year-old Japanese man was referred to our clinic because of bilateral fundus lesions. He had a history of chronic kidney disease (CKD) and secondary hyperparathyroidism. Fundus photography showed a cluster of choroidal folds in the superotemporal extra-macular region OS. Swept-source optical coherence tomography demonstrated ellipsoid zone disruption OD, retinal pigment epithelium undulation OS, dilated Haller layer veins OU, and central choroidal thickening OU and thinning of the overlying choroid due to scleral elevation OS. Fluorescein angiography detected macular hyperfluorescence OD. Indocyanine green angiography demonstrated choroidal vascular hyperpermeability together with numerous scattered hypofluorescent lesions OU. Fundus autofluorescence showed multiple hypoautofluorescent spots surrounded by hyperautofluorescent areas OD. Laser speckle flowgraphy exhibited choroidal blood flow reduction represented by a cold color pattern OU. B-mode echography displayed hyperechoic solid lesions with acoustic shadowing and orbital computed tomography revealed high density areas in the sclera, both of which were consistent with calcification. The patient was diagnosed with SCC, and these imaging findings remained unchanged 7 months after the diagnosis. CONCLUSIONS: We reported a case of SCC with the background of CKD. Our detailed multimodal observations indicated choroidal hypoperfusion possibly caused by mechanical compression due to calcium deposition in the sclera.
  • Keiji Kataoka, Satoru Kase, Kousuke Noda, Susumu Ishida
    Ophthalmology. Retina 4 11 1123 - 1124 2020年06月18日 [査読有り][通常論文]
  • Satoru Kase, Hiroaki Endo, Mitsuo Takahashi, Yuki Ito, Michiyuki Saito, Masahiko Yokoi, Satoshi Katsuta, Shozo Sonoda, Taiji Sakamoto, Susumu Ishida, Manabu Kase
    Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 258 5 971 - 977 2020年05月 [査読有り][通常論文]
     
    PURPOSE: The aim of this study was to analyze choroidal structures in healthy subjects and patients with/without diabetic macular edema (DME). METHODS: This was a retrospective observation case control study. Four hundred and two eyes of patients with diabetes mellitus (DM), and 124 age-matched eyes of healthy subjects were enrolled in this study. DM patients were divided into 3 groups: presence of central-involved (CI) DME (n = 81) and nonCI-DME/non-DME (n = 321), based on OCT findings. Central choroidal thickness (CCT) and total choroidal, luminal, and stromal areas were determined using EDI-OCT and a binarization method, respectively. The luminal area expressed as a ratio of the total choroidal area was defined as the L/C ratio. RESULTS: DM eyes showed a significantly lower L/C ratio than control eyes, whereas there was no significant difference in CCT or total choroidal, luminal, or stromal areas. There was no significant difference between CI-DME and non-DME groups in HbA1c, blood pressure, dyslipidemia, or renal function. CCT and total choroidal, luminal, and stromal areas were significantly greater in the CI-DME group than non-DME group (each P < 0.05). CONCLUSIONS: These results suggest that CCT was thickened in the presence of DME, associated with both increased luminal and stromal areas, which might be related to the pathology of DME.
  • Yuka Suimon, Satoru Kase, Ichiro Miura, Kan Ishijima, Susumu Ishida
    Anticancer research 40 4 2019 - 2023 2020年04月 [査読有り][通常論文]
     
    BACKGROUND/AIM: CD38 is a cell surface marker commonly present in plasma cells and activated T cells, while CD138 is a representative plasma cell marker. The aim of this study was to describe the expression of cell surface markers including CD38 and CD138, in the tumors of patients with IgG4-related ophthalmic disease (IgG4-ROD) and extranodal marginal zone B-cell lymphoma (EMZL) of the ocular adnexa. MATERIALS AND METHODS: Twenty-four consecutive patients of whom 12 had IgG4-ROD and 12 EMZL were enrolled in this study. Medical records were reviewed for flow cytometry (FCM) results on conventional T-cell markers, B-cell markers, CD38 and CD138. RESULTS: Positive rates of T-cell markers, CD38 and CD138 were significantly higher in IgG4-ROD than in EMZL (p<0.01 and p<0.05, respectively). CONCLUSION: Our FCM results on CD38 and CD138 showed that the lymphocyte populations were different between IgG4-ROD and EMZL, which may reflect the different pathophysiology of the two diseases.
  • Kanae Fukutsu, Kenichi Namba, Daiju Iwata, Kazuomi Mizuuchi, Satoru Kase, Kayo Suzuki, Hiroshi Shimizu, Yukiko Shibata, Fumihiko Yamawaki, Masahiro Onozawa, Susumu Ishida
    BMC ophthalmology 20 1 94 - 94 2020年03月10日 [査読有り][通常論文]
     
    BACKGROUND: Hematologic malignancies occasionally cause serous retinal detachment (SRD); however, its pathogenesis remains unclear. Here we present the imaging characteristics of metastatic choroidal lymphoma masquerading as Vogt-Koyanagi-Harada (VKH) disease. CASE PRESENTATION: A 45-year-old Japanese woman was referred to our clinic because of bilateral SRD with blurred vision. Fluorescein angiography revealed multiple pinpoint leakage followed by pooling OU. Enhanced depth imaging optical coherence tomography showed marked choroidal thickening OU. Laser speckle flowgraphy detected choroidal circulation impairment OU. Although these results totally agreed with the inflammatory manifestations of acute VKH disease, indocyanine green angiography demonstrated various sizes of sharply marginated hypofluorescent lesions that seemed atypical for the finding of VKH disease, i.e., vaguely marginated hypofluorescent small dots. Cerebrospinal fluid pleocytosis was not detected. Blood tests revealed leukocytosis together with elevation of lactate dehydrogenase and soluble interleukin-2 receptor levels. Corticosteroid pulse therapy did not improve any ocular findings. Bone marrow biopsy was then performed, leading to a definite diagnosis of diffuse large B-cell lymphoma. After starting systemic chemotherapy, both SRD and choroidal thickening resolved rapidly with visual recovery. However, choroidal hypoperfusion persisted, which contrasted distinctly with the inflammatory pattern of VKH disease, i.e., the restoration of choroidal blood flow in parallel with normalization of choroidal thickness. CONCLUSIONS: Our detailed multimodal observations highlighted the differential imaging features of choroidal lymphoma despite close resemblance to VKH disease especially at the initial stage. Impaired circulation in the thickened choroid marked the pseudo-inflammatory pathogenesis of SRD due to choroidal involvement with neoplastic, but not inflammatory cells.
  • Waardenburg症候群と網膜芽細胞腫を合併した13番染色体長腕部分欠失の1例
    赤岡 さくら, 安藤 亮, 加瀬 諭, 外木 秀文, 長 祐子, 藤井 史彦, 太田 亨, 石田 晋
    日本眼科学会雑誌 124 臨増 231 - 231 (公財)日本眼科学会 2020年03月
  • SDT fattyラット水晶体におけるポリオール経路と酸化ストレスの継時的解析
    菊地 香澄, 村田 美幸, 野田 航介, 神田 敦宏, 加瀬 諭, 影山 靖, 篠原 雅巳, 笹瀬 智彦, 石田 晋
    日本眼科学会雑誌 124 臨増 242 - 242 (公財)日本眼科学会 2020年03月
  • Waardenburg症候群と網膜芽細胞腫を合併した13番染色体長腕部分欠失の1例
    赤岡 さくら, 安藤 亮, 加瀬 諭, 外木 秀文, 長 祐子, 藤井 史彦, 太田 亨, 石田 晋
    日本眼科学会雑誌 124 臨増 231 - 231 (公財)日本眼科学会 2020年03月
  • Satoru Kase, Hiroaki Endo, Mitsuo Takahashi, Michiyuki Saito, Masahiko Yokoi, Yuki Ito, Satoshi Katsuta, Shozo Sonoda, Taiji Sakamoto, Susumu Ishida, Manabu Kase
    The British journal of ophthalmology 104 3 417 - 421 2020年03月 [査読有り][通常論文]
     
    PURPOSE: The aim of this study was to analyse choroidal structures in normal patients and patients with diabetes with various severities of diabetic retinopathy (DR). METHODS: This is a retrospective observation case control study. Three hundred and forty-two diabetic eyes, and age-matched 112 eyes without diabetes mellitus (DM) were enrolled in this study. Patients with DM were classified into no DR, mild/moderate non-proliferative DR (mNPDR), severe NPDR and proliferative DR (PDR). Patients with DM were further divided into two groups based on information regarding systemic DM treatment situation: DM-treated and untreated groups. Central choroidal thickness (CCT), and total choroidal area (TCA), luminal area (LA) and stromal area (SA) were determined using enhanced depth imaging optical coherence tomography and a binarisation method, respectively. The ratio of LA in the TCA was defined as L/C ratio. RESULTS: The haemoglobin A1c (HbA1c) value was significantly higher in the DM-untreated than in the DM-treated subjects. L/C ratio was significantly lower in all the diabetic eyes than control eyes (p<0.05). TCA, LA, L/C ratio and CCT were significantly greater in the DM-untreated than treated group (each p<0.05). In the DM-untreated group, TCA and LAs (p<0.05) and L/C ratio (p<0.01) were significantly lower in mNPDR subjects than normal controls (p<0.05). PDR in the DM-untreated group showed significantly larger SA and LA, and greater CCT than normal controls (each p<0.05). CONCLUSIONS: These results suggest that choroidal vasculature was initially involved at an early DR, whereas thickened LA and SA were noted in advanced DR.
  • Mizuki Tagami, Norihiko Misawa, Saki Noma-Ishikura, Satoshi Honda, Satoru Kase, Shigeru Honda
    Retinal cases & brief reports 16 3 375 - 378 2020年02月13日 [査読有り][通常論文]
     
    PURPOSE: To describe the immunohistochemical profile in a case with focal nodular gliosis (FNG) of the retina. METHODS: A 56-year-old female patient presented with vitreoretinal tractional syndrome with FNG of the retina. After resection of the retinal tumor tissue during the 25-G pars plana vitrectomy, immunohistochemistry using anti-epidermal growth factor receptor (EGFR), p-53, Ki67, glial fibrillary acid protein (GFAP), CD34, and vascular endothelial growth factor antibodies was performed in the excised tissue of the FNG of the retina. RESULTS: Histopathological analysis of the tumor led to a diagnosis of FNG of the retina. Spindle cells of the tumor exhibited strong positive staining for glial fibrillary acid protein, and there was local staining for CD34 in the endothelial cells in the blood vessels. The epidermal growth factor receptor and vascular endothelial growth factor immunoreactivity were strongly observed in the endothelial cells. CONCLUSION: This study demonstrated epidermal growth factor receptor expression in eyes with FNG of the retina. Oncogenic epidermal growth factor receptor might trigger and amplify the expression and function of endothelial vascular endothelial growth factor.
  • 新海 晃弘, 加瀬 諭, 山下 優, 森 祥平, 安藤 亮, 藤谷 顕雄, 鈴木 智浩, 野田 航介, 石田 晋
    あたらしい眼科 37 2 230 - 234 (株)メディカル葵出版 2020年02月 
    背景:運転席用supplemental restraint system(SRS)エアバッグは、最高時速約300kmで運転手に向かって展開し、それに伴う臓器障害は多岐にわたる。本稿では、SRSエアバッグ展開に伴い網膜再剥離と気胸を発症した症例の臨床経過を報告する。症例:73歳、男性。北海道大学病院眼科で左眼裂孔原性網膜剥離(RRD)に対する水晶体再建術、硝子体手術および輪状締結術後の経過観察中に、展開するSRSエアバッグで受傷した。受傷2週間後に再診し、左眼のRRDの再発があり、硝子体手術およびシリコーンオイルタンポナーデを施行した。術後8日目に、突然の胸痛と動悸を発症した。右気胸と診断され、治療された。受傷後12ヵ月の現在、全身状態は安定しており、網膜再剥離はない。結論:SRSエアバッグ作動に伴う外傷は、網膜再剥離のリスクになると同時に、全身合併症を伴うこともあるため注意が必要である。(著者抄録)
  • Supplemental Restraint Systemエアバッグによる網膜再剥離と気胸を発症した1例
    新海 晃弘, 加瀬 諭, 山下 優, 森 祥平, 安藤 亮, 藤谷 顕雄, 鈴木 智浩, 野田 航介, 石田 晋
    あたらしい眼科 37 2 230 - 234 (株)メディカル葵出版 2020年02月 [査読有り][通常論文]
     
    背景:運転席用supplemental restraint system(SRS)エアバッグは、最高時速約300kmで運転手に向かって展開し、それに伴う臓器障害は多岐にわたる。本稿では、SRSエアバッグ展開に伴い網膜再剥離と気胸を発症した症例の臨床経過を報告する。症例:73歳、男性。北海道大学病院眼科で左眼裂孔原性網膜剥離(RRD)に対する水晶体再建術、硝子体手術および輪状締結術後の経過観察中に、展開するSRSエアバッグで受傷した。受傷2週間後に再診し、左眼のRRDの再発があり、硝子体手術およびシリコーンオイルタンポナーデを施行した。術後8日目に、突然の胸痛と動悸を発症した。右気胸と診断され、治療された。受傷後12ヵ月の現在、全身状態は安定しており、網膜再剥離はない。結論:SRSエアバッグ作動に伴う外傷は、網膜再剥離のリスクになると同時に、全身合併症を伴うこともあるため注意が必要である。(著者抄録)
  • Hiroaki Endo, Satoru Kase, Mitsuo Takahashi, Michiyuki Saito, Masahiko Yokoi, Chisato Sugawara, Satoshi Katsuta, Susumu Ishida, Manabu Kase
    PloS one 15 1 e0226630  2020年 [査読有り][通常論文]
     
    PURPOSE: To investigate the relationship between diabetic macular edema (DME) and the choroidal layer thickness in diabetic patients. METHODS: This is a retrospective observation study. Three hundred eighteen eyes of 159 diabetes mellitus (DM) patients and age-matched 100 eyes of 79 healthy controls were enrolled. DME was defined as over 300 μm in the central retinal subfield of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid sector. The central choroidal thickness (CCT), as well as inner and outer layers were determined based on enhanced depth imaging (EDI)-OCT. Diabetic patients with/without systemic diabetic treatments (DT) at the start of this study was defined as DT+ and DT-, respectively. The number of eyes examined was 62 and 256 eyes in DME+and DME-groups, respectively. DM patients were further subdivided into 4 groups with/without DME and DT; DME+DT+(35 eyes), DME-DT+(159 eyes), DME+DT-(27 eyes), and DME-DT-group (97 eyes). Multiple comparisons on CCT layers including control and each DM group were statistically examined. RESULTS: The total CCT layer was 254±83, 283±88, and 251±70 μm in the control, DME+, and DME-group, respectively. A total CCT layer in DME+was significantly thicker than the DME-group (P < 0.05). The outer CCT layer was 195±75, 222±83, and 193±63 μm in the control, DME+, and DME-group, respectively. The outer CCT layer in DME+ was significantly thicker than the DME-group (P < 0.05). In the subdivided groups, the total CCT layers in the control, DME+DT+, DME-DT+, DME+DT-and DME-DT-groups were 254±83, 274±88, 247±66, 290±84 and 258±75 μm, respectively. The outer CCT layers in each group were 195±75, 214±83, 189±58, 228±77, and 201±70 μm, respectively. Total CCT and the outer layer in DME+DT-was significantly thicker than the DME-DT+group (each P < 0.05). In contrast, there was no significant difference in inner layer between the groups. CONCLUSIONS: The total and outer CCT layers of diabetic eyes were significantly thickened in the DME+DT-as compared with the DME-DT+group, suggesting that CCT may be related to the pathology of DME.
  • Satoru Kase, Shinki Chin, Teruhiko Hamanaka, Yasuhiro Shinmei, Takeshi Ohguchi, Susumu Ishida
    International journal of ophthalmology 13 7 1167 - 1169 2020年 [査読有り][通常論文]
  • Kasumi Kikuchi, Miyuki Murata, Kousuke Noda, Satoru Kase, Yoshiaki Tagawa, Yasushi Kageyama, Masami Shinohara, Tomohiko Sasase, Susumu Ishida
    Journal of diabetes research 2020 3058547 - 3058547 2020年 [査読有り][通常論文]
     
    Spontaneously Diabetic Torii (SDT) fatty rat is a novel animal model of type 2 diabetes with obesity. SDT fatty rats develop hyperglycemia, dyslipidemia, and other diabetic complications including ocular disorders; however, diabetic cataract formation in SDT fatty rats has not been fully investigated. The aim of the current study was to investigate the characteristics of cataract in the SDT fatty rats. The mean body weight of SDT fatty rats is larger than that of age-matched Sprague-Dawley (SD) rats and control animals until 8 weeks of age, and thereafter the growing speed decreased until the end of observation at 16 weeks of age. Blood glucose levels in SDT fatty rats were significantly higher than those in SD rats throughout the observational period. Slit-lamp examination revealed that no rats showed cataract formation at 5 weeks of age; however, SDT fatty rats gradually developed cortical cataract and posterior subcapsular cataract, both of which are the common types of cataract in patients with type 2 diabetes. The levels of glucose, sorbitol, and fructose were higher in the lens tissues of SDT fatty rats in comparison with that of SD rats. Furthermore, the level of 4-hydroxynonenal (4-HNE) was higher in the lens of SDT fatty rats than in that of SD rats. By contrast, total glutathione (GSH) concentration was lower in the lens of SDT fatty rats than in that of SD rats. The present study demonstrated that the cataractogenesis in SDT fatty rats resembled human diabetic cataract formation, indicating that SDT fatty rats serve as a potential animal model in researches on human cataract associated with type 2 diabetes and obesity.
  • ポリープ状脈絡膜血管症に対する光線力学的療法トリプル療法の5年成績
    安藤 亮, 野田 航介, 廣岡 季里子, 柴田 有紀子, 橋本 勇希, 鈴木 智浩, 清水 啓史, 藤谷 顕雄, 董 震宇, 加瀬 諭, 吉澤 史子, 齋藤 航, 石田 晋
    眼科臨床紀要 12 11 832 - 832 眼科臨床紀要会 2019年11月
  • 網膜変性を認めたDanon病の1例
    長谷川 綾華, 藤谷 顕雄, 柴田 有紀子, 鈴木 智浩, 清水 啓史, 董 震宇, 加瀬 諭, 野田 航介, 石田 晋
    眼科臨床紀要 12 11 854 - 854 眼科臨床紀要会 2019年11月
  • 術後細菌性眼内炎との鑑別を要した水晶体起因性眼内炎の1例
    清水 啓史, 加瀬 諭, 柴田 有紀子, 鈴木 智浩, 董 震宇, 藤谷 顕雄, 野田 航介, 石田 晋
    眼科臨床紀要 12 11 856 - 856 眼科臨床紀要会 2019年11月
  • Ye Liu, Atsuhiro Kanda, Di Wu, Erdal Tan Ishizuka, Satoru Kase, Kousuke Noda, Atsuhiro Ichihara, Susumu Ishida
    Molecular therapy. Nucleic acids 17 113 - 125 2019年09月06日 [査読有り][通常論文]
     
    The receptor-associated prorenin system refers to the pathogenic mechanism whereby prorenin binding to (pro)renin receptor [(P)RR] dually activates the tissue renin-angiotensin system (RAS) and RAS-independent signaling, and its activation contributes to the molecular pathogenesis of various ocular diseases. We recently developed a new single-stranded RNAi agent targeting both human and mouse (P)RR ((P)RR-proline-modified short hairpin RNA [(P)RR-PshRNA]), and confirmed its therapeutic effect on murine models of ocular inflammation. Here, we investigated the efficacy of (P)RR-PshRNA against laser-induced choroidal neovascularization (CNV) and subretinal fibrosis, both of which are involved in the pathogenesis of age-related macular degeneration (AMD). Administration of (P)RR-PshRNA in mice significantly reduced CNV formation, together with the expression of inflammatory molecules, macrophage infiltration, and extracellular signal-regulated kinase (ERK) 1/2 activation. In addition, (P)RR-PshRNA attenuated subretinal fibrosis, together with epithelial-mesenchymal transition (EMT)-related markers including phosphorylated SMAD2. The suppressive effect of (P)RR-PshRNA is comparable with aflibercept, an anti-vascular endothelial growth factor drug widely used for AMD therapy. AMD patient specimens demonstrated (P)RR co-localization with phosphorylated ERK1/2 in neovascular endothelial cells and retinal pigment epithelial cells. These results indicate that (P)RR contributes to the ocular pathogenesis of both inflammation-related angiogenesis and EMT-driven fibrosis, and that (P)RR-PshRNA is a promising therapeutic agent for AMD.
  • 網膜上下の増殖組織が連続していた黄斑円孔網膜剥離併発の増殖糖尿病網膜症の1例
    柴田 有紀子, 清水 啓史, 長谷川 綾華, 品川 真有子, 齋藤 理幸, 加瀬 諭, 野田 航介, 石田 晋
    糖尿病合併症 33 Suppl.1 266 - 266 (一社)日本糖尿病合併症学会 2019年09月
  • Spontaneously Diabetic Torii fattyラット網膜における炎症性サイトカインの発現解析
    菊地 香澄, 野田 航介, 村田 美幸, 神田 敦宏, 加瀬 諭, 影山 靖, 篠原 雅巳, 笹瀬 智彦, 石田 晋
    糖尿病合併症 33 Suppl.1 271 - 271 (一社)日本糖尿病合併症学会 2019年09月
  • 抗α-enolase抗体陽性自己免疫性網膜症の網膜電図所見
    安藤 亮, 齋藤 航, 神田 敦宏, 加瀬 諭, 藤波 芳, 菅原 道孝, 中村 洋介, 江口 秀一郎, 野田 航介, 篠田 啓, 石田 晋
    眼科臨床紀要 12 8 642 - 643 眼科臨床紀要会 2019年08月 [査読有り][通常論文]
  • Hiroaki Endo, Satoru Kase, Yuki Ito, Mitsuo Takahashi, Masahiko Yokoi, Satoshi Katsuta, Shozo Sonoda, Taiji Sakamoto, Susumu Ishida, Manabu Kase
    Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 257 6 1133 - 1140 2019年06月 [査読有り][通常論文]
     
    BACKGROUND: The aim of this study was to evaluate the relationship between the choroidal structure of diabetic patients without diabetic retinopathy (DR) and duration of diabetes. METHODS: This study is a retrospective observational study in diabetic patients without DR. Eyes with diabetes mellitus (DM) (n = 105) were divided into two groups based on the duration: long duration group (over 10 years, n = 31) and short duration group (less than 10 years, n = 74). One hundred seventeen eyes of non-diabetic patients were used as control group. All patients underwent enhanced depth imaging optical coherence tomography, and the choroidal structure was analyzed using a binarization method. RESULTS: There was no significant difference in areas of total choroid and lumina/stroma or central choroidal thickness (CCT) between control and DM groups. In contrast, lumina/total choroidal (L/C) ratio was significantly lower in diabetic eyes than in control eyes (P = 0.02). Although there was no significant difference in the areas or CCT between short and long duration groups, L/C ratio was significantly lower in the long duration group than in the short duration group (P = 0.03). CONCLUSIONS: The current study suggests that choroidal vasculature is involved in the diabetic eyes and that the choroidal structure has changed with duration of diabetes. Our study points out that L/C ratio is a new potential biomarker in monitoring choroidal vascular disorders in diabetic eyes without DR.
  • Satoru Kase, Susumu Ishida
    Molecular and clinical oncology 10 5 521 - 523 2019年05月 [査読有り][通常論文]
     
    von Hippel Lindau (VHL) disease is caused by inactivation of the VHL tumor suppressor gene, resulting in formation of multiple systemic tumors. Juxtapapillary retinal capillary hemangioma (JRCH) is one of the major manifestations in VHL disease; however, treatments are challenging, especially in children. The present study reports the case of a 6-year-old girl with suspected VHL disease presenting with JRCH. Fluorescein angiography demonstrated marked dye leakage from the tumor. Retinal hemorrhage occurred around the tumor 7 months later. Laser photocoagulation of the tumor tissue was safely and successfully conducted without general anesthesia. The hemorrhage diminished after laser photocoagulation. Optical coherence tomography demonstrated mild resolution of an elevated lesion in JRCH with contraction of the vitreoretinal interface over the tumor. Laser photocoagulation may be considered the first-line treatment for young patients with JRCH, although the primary physicians must have the necessary skills and be able to establish good doctor-patient relationships, even with children.
  • Iku Kikuchi, Satoru Kase, Yuki Hashimoto, Kiriko Hirooka, Susumu Ishida
    Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 257 4 835 - 841 2019年04月 [査読有り][通常論文]
     
    PURPOSE: This study aims to examine the relationship between ocular circulation changes and visual field defects in optic disk melanocytoma (ODM). METHODS: Five eyes of five patients were enrolled in this study. All patients were diagnosed with ODM in the Department of Ophthalmology, Hokkaido University Hospital from March 2009 to November 2017. Ophthalmological data including optical coherence tomography angiography (OCTA) and laser speckle flowgraphy (LSFG) findings were retrospectively analyzed. RESULTS: The five ODM cases consisted of two females and three males. Ages of the patients ranged from 47 to 82 years (mean 54 years). Follow-up periods were from 4 to 105 months. Fluorescein angiography showed hypo-fluorescence throughout the examination in all four eyes examined with this modality. OCTA detected dense blood vessel networks in the tumor in two out of the five eyes. Nasal visual field defects were found in two other eyes, which were correlated with locations of tumors free of vessel networks. One ODM eye without marked visual field defects and pigmentations showed lower mean blur rates determined by LSFG in optic disk vessels and tissue circulations than those in the contralateral eye. During follow-up, there was no tumor enlargement in any case. CONCLUSIONS: This study showed the relationship between the deficit of blood vessel networks and visual field defects in ODM patients. LSFG demonstrated reduced blood flow in the tumor, suggesting that circulatory disorder caused by the optic disk tumor might be correlated with visual field defect.
  • Spontaneously Diabetic Torii fattyラットにおける糖尿病白内障の検討
    菊地 香澄, 野田 航介, 村田 美幸, 田川 義晃, 神田 敦宏, 加瀬 諭, 影山 靖, 篠原 雅巳, 笹瀬 智彦, 石田 晋
    日本眼科学会雑誌 123 臨増 166 - 166 (公財)日本眼科学会 2019年03月
  • Yukiko Shibata, Satoru Kase, Kenichi Namba, Susumu Ishida
    International journal of ophthalmology 12 4 685 - 688 2019年 [査読有り][通常論文]
  • Takita A, Hashimoto Y, Saito W, Kase S, Ishida S
    American journal of ophthalmology case reports 12 68 - 72 2018年12月 [査読有り][通常論文]
  • Acute macular neuroretinopathyにおける脈絡膜層別厚の経時変化
    橋本 勇希, 齋藤 航, 滝田 亜かり, 長谷川 裕香, 鈴木 智浩, 安藤 亮, 藤谷 顕雄, 森 祥平, 加瀬 諭, 野田 航介, 石田 晋
    眼科臨床紀要 11 11 836 - 837 眼科臨床紀要会 2018年11月
  • MPO-ANCA陽性を示したparacentral acute middle maculopathyの1例
    福津 佳苗, 安藤 亮, 新明 康弘, 鈴木 智浩, 藤谷 顕雄, 森 祥平, 加瀬 諭, 阿部 早和子, 齋藤 航, 野田 航介, 石田 晋
    眼科臨床紀要 11 11 837 - 837 眼科臨床紀要会 2018年11月
  • エアバッグによる網膜再剥離と気胸を発症した1例
    新海 晃弘, 加瀬 諭, 森 祥平, 安藤 亮, 藤谷 顕雄, 鈴木 智浩, 野田 航介, 石田 晋
    眼科臨床紀要 11 11 846 - 846 眼科臨床紀要会 2018年11月
  • Wu D, Kanda A, Liu Y, Kase S, Noda K, Ishida S
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology 33 2 fj201801227R - 2513 2018年10月 [査読有り][通常論文]
     
    VEGFA and TGF-β are known major angiogenic and fibrogenic factors. Galectin-1, encoded by lectin, galactoside-binding, soluble ( LGALS) 1, has attracted growing attention for its facilitatory role in angiogenesis and fibrosis through its modification of VEGFA and TGF-β receptor signaling pathways. We reveal galectin-1 involvement in the mouse model of laser-induced choroidal neovascularization (CNV) and subretinal fibrosis, both of which represent the pathogenesis of age-related macular degeneration (AMD). Neither deletion nor overexpression of Lgals1 affected physiologic retinal development or visual function. Galectin-1/ Lgals1 was upregulated by CNV induction, whereas deletion of Lgals1 suppressed CNV together with downstream molecules of VEGF receptor (VEGFR)2. Loss of Lgals1 also attenuated subretinal fibrosis, expression of epithelial-mesenchymal transition (EMT) markers including Snai1, and phosphorylation of SMAD family member 2. Supporting these in vivo findings, silencing of LGALS1 in human retinal pigment epithelial (RPE) cells inhibited TGF-β1-induced EMT-related molecules and cell motilities. Conversely, overexpression of Lgals1 enhanced CNV and subretinal fibrosis. Specimens from patients with AMD demonstrated colocalization of galectin-1 with VEGFR2 in neovascular endothelial cells and with phosphorylated SMAD2 in RPE cells. These results suggested a biologic significance of galectin-1 as a key promotor for both angiogenesis and fibrosis in eyes with AMD.-Wu, D., Kanda, A., Liu, Y., Kase, S., Noda, K., Ishida, S. Galectin-1 promotes choroidal neovascularization and subretinal fibrosis mediated via epithelial-mesenchymal transition.
  • Kase S, Namba K, Kanno-Okada H, Onozawa M, Hidaka D, Iwata D, Mizuuchi K, Fukuhara T, Fukuhara J, Kitaichi N, Matsuno Y, Ishida S
    Ocular immunology and inflammation 1 - 9 2018年10月 [査読有り][通常論文]
  • Ando R, Saito W, Kanda A, Kase S, Fujinami K, Sugahara M, Nakamura Y, Eguchi S, Mori S, Noda K, Shinoda K, Ishida S
    American journal of ophthalmology 196 181 - 196 2018年09月 [査読有り][通常論文]
     
    PURPOSE: To evaluate clinical features of Japanese patients with anti-α-enolase antibody-positive autoimmune retinopathy (anti-enolase AIR). DESIGN: Multicenter retrospective observational case series. METHODS: Forty-nine eyes of 25 Japanese anti-enolase AIR patients (16 female and 9 male; mean age at first visit, 60.8 years) were included. Fundus characteristics, perimetry, spectral-domain optical coherence tomography (SD-OCT), electroretinography (ERG), best-corrected visual acuity (BCVA), and complicating systemic tumors were assessed. Protein localization of α-enolase was examined by immunohistochemistry in an enucleated eye of 1 patient. RESULTS: Patients were classified into 3 groups: multiple drusen (48%), retinal degeneration (36%), and normal fundus (16%). Drusen varied in size from small deposits to vitelliform-like lesions. Images on SD-OCT revealed dome-shaped hyperreflectivity beneath the retinal pigment epithelium (RPE), corresponding to drusen. Perimetry showed that ring scotoma was the most frequent (39%). Rod-system and/or single-flash cone responses revealed decreased responses in 81% of the eyes. Combined rod and cone system responses demonstrated significantly lower a-wave amplitudes in the degeneration group than in the drusen group (P = .005). BCVA was improved or maintained in 80% of the eyes during follow-up. Malignant or benign tumors were detected in 30% of patients. The RPE and photoreceptor layers were immunopositive for α-enolase. CONCLUSIONS: The drusen subtype, scarcely described in the literature, is suggested to characterize Japanese patients with anti-enolase AIR. The different funduscopic features with different functional severities may have resulted from antibody-mediated damage to RPE as well as photoreceptor cells.
  • 糖尿病網膜症の増殖組織における分子シャペロンαB-クリスタリンのリン酸化
    加瀬 諭, 董 陽子, 神田 敦宏, 野田 航介, 石田 晋
    日本糖尿病眼学会誌 22 133 - 133 日本糖尿病眼学会 2018年09月
  • Kanae Fukutsu, Satoru Kase, Kan Ishijima, Rumiko Kinoshita, Susumu Ishida
    Radiation Oncology 13 1 95  2018年05月16日 [査読有り][通常論文]
     
    Background: To examine the clinical features of radiation cataract in patients with ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma. Methods: Twenty-one patients with 26 eyes diagnosed with ocular adnexal MALT lymphoma (26 eyes), who were treated in Hokkaido University Hospital, were retrospectively reviewed based on medical records. Results: Out of the 21 patients, 16 patients (21 eyes) received radiation therapy (RT) with a total dose of 30 Gy. All cases eventually achieved complete remission. Eight of these patients (11 eyes: 52.3%) required cataract surgery after RT. The mean age at surgery was 56.8 (40-70) years. The mean latency between RT and the indication for surgery was 43.3 months. The percentage of females was significantly higher in patients who required surgery (P < 0.01), compared with those without surgery. The eyes of patients who received bolus technique on radiation treatment developed cataract more frequently (P < 0.05). In contrast, none of the patients without RT required cataract surgery. Conclusions: Patients with ocular adnexal MALT lymphoma who underwent surgery for radiation cataract were seen more often in relatively young, female patients, and surgery was required about 3 years after RT. A long-term observation may be needed for patients after RT for a tumor. A female sex and the bolus technique may be risk factors for radiation cataract.
  • Endo H, Kase S, Takahashi M, Yokoi M, Isozaki C, Katsuta S, Kase M
    Clinical & experimental ophthalmology 2018年05月 [査読有り][通常論文]
  • Satoru Kase, Shohei Mori, Kousuke Noda, Susumu Ishida
    International Journal of Ophthalmology 11 2 343 - 345 2018年 [査読有り][通常論文]
  • Tanaka A, Saito W, Kase S, Ishijima K, Noda K, Ishida S
    Journal of ophthalmology 2018 5680503 - 5680503 2018年 [査読有り][通常論文]
     
    Purpose: To evaluate the surgical outcomes of pars plana vitrectomy (PPV) with epipapillary membrane removal in patients with maculopathy associated with cavitary optic disc anomalies. Methods: Eight patients (8 eyes) with cavitary optic disc anomaly-associated maculopathy who underwent PPV with epipapillary membrane removal were retrospectively reviewed. The best-corrected visual acuity (BCVA) and macular and papillary morphologies using enhanced depth imaging optical coherence tomography (EDI-OCT) were evaluated before and after treatment. Immunohistochemistry for an intraoperatively excised epipapillary membrane tissue was also performed. Results: Before surgery, EDI-OCT revealed that epipapillary membrane was observed in all patients. Retinoschisis was resolved with no recurrence in all patients following vitrectomy regardless of a disease type or the presence or absence of preoperative posterior vitreous detachment. The mean final BCVA and central retinal thickness significantly improved compared with pretreatment values (P = 0.008 and 0.004, resp.). Immunoreactivity for S100 protein and glial fibrillary acidic protein, markers of astrocytes, was positive in the resected membrane tissues. Conclusions: These results suggest that epipapillary membrane is involved in the pathogenesis of some patients with cavitary optic disc anomaly-associated maculopathy as well as posterior hyaloid membrane. PPV with epipapillary membrane removal may be a useful treatment option for this maculopathy. This trial is registered with UMIN000011123.
  • Suimon Y, Kase S, Ishijima K, Kanno-Okada H, Ishida S
    International journal of ophthalmology 11 9 1539 - 1544 2018年 [査読有り][通常論文]
  • Ishiguro Y, Homma S, Yoshida T, Ohno Y, Ichikawa N, Kawamura H, Hata H, Kase S, Ishida S, Okada-Kanno H, Hatanaka KC, Taketomi A
    Surgical case reports 3 1 71 - 71 Springer 2017年12月 [査読有り][通常論文]
     
    Background: Muir-Torre syndrome (MTS) is a rare autosomal dominant genodermatosis caused by mutations in mismatch repair genes. It is characterized by the presence of at least one sebaceous skin tumor associated with internal malignancies. Whether positron emission tomography/computed tomography (PET/CT) is useful for the detection of malignancies in patients with MTS has not been determined. We herein report two cases in which PET/CT was useful for the diagnosis and follow-up of internal malignancies in patients with MTS. Case presentation: In case 1, a 57-year-old woman underwent excision of a sebaceous carcinoma on the left upper eyelid. She underwent follow-up PET/CT once yearly thereafter. Forty-two months after the eyelid surgery, PET/CT showed intense tracer uptake in the right lower abdomen. An ascending colon tumor was identified, and examination of a biopsy specimen showed adenocarcinoma. In case 2, a 77-year-old man presented for evaluation of three continuous papules with telangiectasia on his right cheek. Examination of a skin biopsy specimen of the cheek papule revealed a sebaceous carcinoma. He underwent PET/CT to detect other malignancies. PET/CT showed intense tracer uptake in the sigmoid colon. A sigmoid colon tumor was identified, and examination of a biopsy specimen showed adenocarcinoma. Both patients underwent resection of their tumors, and both were still free of recurrence of the sebaceous and colon carcinomas at the time of this writing. Conclusion: PET/CT is a reliable imaging modality for the detection of internal malignancies and is useful for the diagnosis and follow-up of MTS.
  • Iku Kikuchi, Satoru Kase, Kan Ishijima, Susumu Ishida
    GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY 255 11 2271 - 2276 2017年11月 [査読有り][通常論文]
     
    The purpose of this study was to report the clinical outcomes of patients with conjunctival melanoma treated with interferon (IFN) alpha-2b eye drops following local tumor resection. Five eyes of five patients were enrolled in this study. All patients underwent the local resection of tumors, and topical IFN alpha-2b eye drops were subsequently administered 4 times/day until the complete disappearance of the pigmented lesions determined by slit-lamp examination. Ophthalmological findings, histopathological findings, and imaging modalities were retrospectively analyzed. The age of the patients ranged from 65 to 84 years (mean: 75.4 years). Locations of the tumor were the bulbar conjunctiva in three eyes, multiple palpebral conjunctivas in one eye, and palpebral conjunctiva and caruncle in one eye. All patients received topical IFN alpha-2b eye drop treatment for 6-10 months. Follow-up periods after resection ranged from 18 to 78 months. Histologically, all excised conjunctival tumors were diagnosed with malignant melanoma, where the surgical margins were completely negative in one patient. No patients had suffered from severe adverse effects related to IFN alpha-2b. Four out of five patients consequently achieved complete remission. Since one eye in one case showed resistance to the local chemotherapy containing IFN alpha-2b eye drops and the subconjunctival injection of IFN-beta, orbital exenteration was eventually required 12 months after local resection. Topical IFN alpha-2b eye drops may be safe and one of the useful adjunctive treatments following surgical resection for patients with conjunctival melanoma.
  • Satoru Kase, Kan Ishijima, Takehiko Uraki, Yuka Suimon, Yasuo Suzuki, Manabu Kase, Susumu Ishida
    ANTICANCER RESEARCH 37 9 5001 - 5004 2017年09月 [査読有り][通常論文]
     
    Background/Aim: Although flow cytometry (FCM) is used to evaluate cell surface markers of various leucocyte populations quantitatively, little is known about the usefulness of FCM in lymphoproliferative disorders of the ocular adnexa. The aim of this study was to disclose results of FCM, which were compared among IgG4-related ophthalmic disease (IgG4-ROD), idiopathic orbital inflammation (IOI), and extranodal marginal zone B-cell lymphoma (EMZL). Materials and Methods: This is a retrospective observational study. Sixty-nine tumors comprising of 16 IgG4-ROD, 24 IOI, and 29 EMZL were enrolled in the study. All tumors, surgically excised, were diagnosed based on histopathology, immunoglobulin (Ig) heavy chain gene rearrangement, and FCM. In FCM, the percentage of T-cell markers (CD2, CD3, CD4, CD5, CD7, CD8), B-cell markers (CD10, CD19, CD20, CD23), NK cell marker (CD56) and cell surface kappa/lambda was searched based on medical records. Ig light chain restriction was evaluated from results in kappa/lambda deviation by FCM. Results: The percentage of CD2, CD3, CD4, CD7, and CD10 was significantly higher in IgG4-ROD/IOI than EMZL (p<0.05 in every factor). In contrast, CD19 and CD20 percentages were significantly greater in EMZL than IgG4-ROD/IOI (p<0.01). There was no significant difference in any marker between IgG4-ROD and IOI. Kappa-positive cells were significantly greater in EMZL than IgG4-ROD/IOI (p<0.05). In kappa/lambda deviation, false-positive was noted in 3 (7.5%) benign IgG4-ROD/IOI and false-negative was observed in 10 (34.5%) EMZL cases. Sensitivity and specificity of Ig light chain restriction were 65.5 and 92.5%, respectively. Conclusion: Analyses of cell surface markers using FCM were useful in differentiating EMZL from IgG4-ROD/IOI. Sensitivity of Ig light chain restriction was relatively low in diagnosis of EMZL using FCM.
  • Hiromi Kanno-Okada, Emi Takakuwa, Yoshiaki Tagawa, Satoru Kase, Kanako C. Hatanaka, Yutaka Hatanaka, Kenichi Namba, Tomoko Mitsuhashi, Yoshihiro Matsuno
    PATHOLOGY INTERNATIONAL 67 7 342 - 349 2017年07月 [査読有り][通常論文]
     
    Intraocular lymphoma is a rare neoplasm that occurs only in the eyes and/or central nervous system. Diagnosis of intraocular lymphoma is difficult because its clinical manifestations mimic chronic uveitis. Pathological examination of the vitreous is one of the main diagnostic tools for intraocular lymphoma, but this is challenging due to the sparse cellularity and specimen degeneration. Here, we reviewed 33 cell block preparations from vitreous perfusion fluid in order to examine the significance of cytopathological findings for differential diagnosis using vitreous samples. The cases comprised 12 intraocular lymphomas and 21 non-lymphomatous diseases. Cytologically, vitreous samples from non-lymphoma cases showed lower cellularity than the lymphoma cases. Whereas vitreous material from cases with infectious endophthalmitis showed prominent neutrophilic infiltration, material from sarcoidosis cases showed infiltration of small lymphoid cells, especially CD4-positive T cells. On the other hand, lymphoma cases showed higher cellularity, with large, irregular and atypical lymphoid cells, frequent necrotic cells in the background, and less pronounced neutrophil infiltration. Immunocytochemically, 11 of the 12 lymphoma cases were of the B-cell phenotype and the remaining case was of the T/NK-cell phenotype. In conclusion, careful cytopathological examination or immunocytochemistry of vitreous material facilitates appropriate diagnosis of intraocular lymphoma.
  • Satoru Kase, Toshiya Shinohara, Manabu Kase, Susumu Ishida
    EXPERIMENTAL AND THERAPEUTIC MEDICINE 13 6 3516 - 3522 2017年06月 [査読有り][通常論文]
     
    It has been demonstrated that topical administration of rebamipide, which is an antiulcer agent, increases the mucin level of the tear film and ameliorates ocular surface conditions such as lid wiper epitheliopathy. The aim of the present study was to analyze the changes in goblet cell number, cell proliferation, and epidermal growth factor receptor (EGFR) induced by topical rebamipide addition to the lid wiper of humans. A total of 30 eyelid tissue samples were obtained during involutional entropion surgeries, fixed in paraformaldehyde, embedded in paraffin and divided into two groups: Rebamipide or non-rebamipide. The tissues in the rebamipide group were obtained from patients who had a medical history of topical rebamipide use prior to surgery. The number of goblet cells was counted under light microscopy. A total of 22 eyelid tissue samples were further examined using immunohistochemistry with anti-Ki-67 and anti-EGFR antibodies to evaluate cell proliferation and EGFR expression, respectively. Histologically, the lid wiper and palpebral conjunctiva were clearly identified in the tissues. The number of goblet cells was significantly higher in the rebamipide group compared with the non-rebamipide group (P=0.0367). There was no significant difference in lid wiper cell proliferation between the rebamipide and non-rebamipide groups. Immunohistochemistry revealed that EGFR levels in the lid wiper epithelial cells were significantly higher in the rebamipide group compared with the non-rebamipide group (P=0.0237). These results suggest that topical rebamipide application increases the number of goblet cells in the lid wiper, which in turn upregulates the expression of EGFR. These findings may be clinically relevant and provide a therapeutic basis for the treatment of ocular disease such as dry eye and lid wiper epitheliopathy.
  • Kase S, Ohguchi T, Ishida S
    Case reports in ophthalmology 8 2 349 - 352 2017年05月 [査読有り][通常論文]
  • Satoru Kase, Toshiya Shinohara, Mika Noda, Susumu Ishida, Manabu Kase
    INTERNATIONAL JOURNAL OF OPHTHALMOLOGY 10 4 656 - 657 2017年04月 [査読有り][通常論文]
  • Daiju Iwata, Kazuomi Mizuuchi, Koki Aoki, Yukihiro Horie, Satoru Kase, Kenichi Namba, Shigeaki Ohno, Susumu Ishida, Nobuyoshi Kitaichi
    OCULAR IMMUNOLOGY AND INFLAMMATION 25 sup1 S15 - S18 2017年 [査読有り][通常論文]
     
    Purpose: Environmental and lifestyle changes influence the clinical features of uveitis. This study reviewed the epidemiologic trends of uveitis in the Japanese population.Methods: A retrospective review of the past 80 years of reports from Hokkaido University Hospital.Results: In the 1930s, tuberculosis accounted for 46% and syphilitic uveitis for 31% of cases. The frequency of these diseases decreased to 12% in the 1950s; 8% in 1969; 0.6% in the 1990s; and 0.8% in the 2000s, while the rate of non-infectious uveitis increased. The three most common specific diagnoses were: sarcoidosis, Vogt-Koyanagi-Harada disease, and Behcet disease. Although Behcet disease was the most frequent non-infectious uveitis until the 1980s, sarcoidosis is now the most frequent cause of newly diagnosed non-infectious uveitis.Conclusions: The etiology of uveitis has changed with the times. Tubercular and syphilitic cases have greatly decreased, and sarcoidosis is the most frequent type of uveitis today.
  • Kase S, Chin S, Hamanaka T, Shinmei Y, Ohguchi T, Kijima R, Matsuda A, Ishida S
    The open ophthalmology journal 11 103 - 106 2017年 [査読有り][通常論文]
     
    PURPOSE: The aim of this study was to report a case of atopic dermatitis showing elevated intraocular pressure (IOP) beyond the baseline levels followed by a modified 360-degree suture trabeculotomy, and to analyze the histological findings in the trabecular meshwork. METHODS: A 40-year-old male suffered from blurred vision in the right eye (OD). He had a medical history of severe atopic dermatitis and intraocular lens implantation OU due to atopic cataract. At the initial presentation, the visual acuity was 0.03, and IOP was 35 mmHg OD. Slit-lamp examination demonstrated corneal epithelial edema OD. Increased IOP was refractory to several topical medications. The patient underwent a modified 360-degree suture trabeculotomy. The visual field defect, however, deteriorated with persistently high IOP. The patient underwent trabeculectomy together with drainage implant surgery. In the outflow routes, although there seemed to be an opening of Schlemm's canal into the anterior chamber, there was no endothelium of the canal in the region of its opening. The fibrotic changes were conspicuous around Schlemm's canal. CONCLUSION: The histological results indicated that trabeculotomy might not be an appropriate treatment for patients with atopic glaucoma, possibly because of excessive repair to the newly created uveoscleral outflow in addition to the increased postoperative fibrosis in the trabecular meshwork and Schlemm's canal.
  • Kase S, Saito W, Mori S, Saito M, Ando R, Dong Z, Suzuki T, Noda K, Ishida S
    Clinical ophthalmology (Auckland, N.Z.) 11 9 - 14 2017年 [査読有り][通常論文]
     
    PURPOSE: The aims of this study were to analyze optical coherence tomography (OCT) imaging of large macular holes (MHs) treated with inverted internal limiting membrane (ILM) flap technique and to perform a histological examination of an ILM-like membrane tissue obtained during vitrectomy. PATIENTS AND METHODS: This is a retrospective observational case study. Nine patients, comprising of five males and four females, showing large and myopic MHs, underwent pars plana vitrectomy (PPV) with inverted ILM flap technique assisted by brilliant blue G (BBG) staining. Ophthalmological findings including visual acuity and OCT were investigated based on medical records. Formalin-fixed paraffin-embedded tissue section of an ILM-like membrane was submitted for immunohistochemistry with glial fibrillary acidic protein (GFAP). RESULTS: ILM was clearly stained with BBG in eight patients, whereas the ILM in one case revealed no staining with BBG during PPV. Visual acuities improved to >0.2 LogMAR in six patients. The complete closure of MH following PPV with inverted ILM technique was eventually achieved in all patients determined by OCT imaging (100%). Only one patient showed recovery of ellipsoid zone and interdigitation zone following the surgery. Elongation of outer nuclear layer was noted in three eyes. The ILM-like membrane not stained with BBG histologically revealed an amorphous structure admixed with GFAP-positive mononuclear cell infiltration. CONCLUSION: PPV with inverted ILM flap technique achieved 100% closure rates with favorable configuration at an initial surgery in large MHs. Our histopathological data also suggest that even BBG staining-negative membrane may be a useful material for autologous transplantation to the hole.
  • Hiroaki Endo, Satoru Kase, Yasuo Suzuki, Manabu Kase
    Case Reports in Ophthalmology 7 3 208 - 212 2016年09月09日 [査読有り][通常論文]
     
    Background: We report a rare case of carcinoma in situ (CIS) in conjunction with a primary pterygium that exhibited characteristic angiographic and histopathological findings. Case: A 78-year-old man presented with a pterygium and a whitish tumor adjacent to the pterygium in his right eye. Indocyanine green angiography displayed that feeder vessels within the primary pterygium spread to the whitish tumor. The tumor and pterygial tissues were surgically removed. Histologically, the resected tissue contained CIS as well as squamous metaplasia. There was a marked inflammatory cell infiltration within the tumor and beneath the epithelium. Topical interferon alfa-2b was given 4 times per day for 2 months. The patient has been well without local recurrence of tumor or distal metastases to 54 follow-up months after surgery. Conclusions: Because CIS can occur adjacent to pterygial tissues, long-term follow-up is necessary in patients with pterygia.
  • 加瀬 諭, 野田 航介
    OCULISTA 41 31 - 38 (株)全日本病院出版会 2016年08月 
    脈絡膜新生血管(CNV)は加齢黄斑変性のみならず、さまざまな炎症疾患、変性疾患に発生し得る。近視性CNVでは、抗VEGF薬治療によりCNVの活動性を制御することが可能であるが、治療後の再発や網脈絡膜萎縮による視力障害が問題である。ぶどう膜炎や点状網膜内層症における炎症性CNVにおいては、副腎皮質ステロイド薬や抗VEGF薬治療がCNVの制御に有用であるが、依然確立された治療法は存在しない。網膜色素線条に伴うCNVに対しては、抗VEGF薬治療により視力を維持することが可能になってきているが、Bruch膜断裂に対する根本的な治療は存在しない。特発性CNVは概して抗VEGF薬治療に対して良好な反応を示すが、治療回数や若年者の中心窩下CNV症例における視力不良例が問題である。以上より、抗VEGF薬治療は、加齢黄斑変性以外のCNVに対しても、有効性を示す眼疾患が多々存在するが、課題も残されている。(著者抄録)
  • Dong Y, Kase S, Dong Z, Fukuhara J, Tagawa Y, Ishizuka ET, Murata M, Shinmei Y, Ohguchi T, Kanda A, Noda K, Ishida S
    International journal of molecular medicine 38 2 545 - 550 2016年08月 [査読有り][通常論文]
     
    Vascular endothelial growth factor C (VEGF-C) plays an important role in the development of a pterygium through lymphangiogenesis. We examined the association between VEGF-C and tumor necrosis factor-α (TNF-α) in the pathogenesis of pterygia. Cultured conjunctival epithelial cells were treated with TNF-α, and the gene expression levels of VEGFC were evaluated by quantitative polymerase chain reaction (qPCR) and VEGF-C protein expression levels were measured using an enzyme-linked immunosorbent assay (ELISA). In addition, using ELISA, we evaluated the VEGF-C protein expression in the supernatants of cultured conjunctival epithelial cells, in which we neutralized TNF-α using anti‑TNF-α antibody. The gene expression of tumor necrosis factor receptor superfamily, member 1A (TNFRSF1A), known as TNF receptor 1 (TNFR1), was confirmed using reverse transcription PCR in cultured conjunctival epithelial cells. Immunofluorescence microscopy was used to examine the localization of VEGF-C and TNFR1 in pterygium tissues and TNFR1 expression in cultured conjunctival epithelial cells. Immunohistochemistry was used to examine the localization of TNFR1 in pterygia and normal conjunctival tissues. VEGFC gene expression increased in cultured conjunctival epithelial cells 24 h after the addition of TNF-α. The secretion of VEGF-C protein was significantly increased 48 h after the stimulation of cultured conjunctival epithelial cells with TNF-α. Increased VEGF-C protein secretion stimulated by TNF-α was significantly reduced by anti-TNF-α neutralizing antibody treatment. In cultured conjunctival epithelial cells, TNFRSF1A and TNFR1 were expressed. TNFR1 was immunolocalized in normal conjunctival tissues and in human pterygium tissues as well as in VEGF‑C‑positive epithelial cells from human pterygia. Our data demonstrate that TNF-α mediates VEGF-C expression, which plays a critical role in the pathogenesis of pterygia.
  • Kase Satoru, Namba Kenichi, Iwata Daiju, Mizuuchi Kazuomi, Kitaichi Nobuyoshi, Tagawa Yoshiaki, Okada-Kanno Hiromi, Matsuno Yoshihiro, Ishida Susumu
    Diagnostic pathology 11 29 - 29 BioMed Central 2016年03月 [査読有り][通常論文]
     
    Background: Vitreoretinal lymphoma (VRL) is a life- and sight-threatening disorder. The aim of this study was to analyze the usefulness of the cell block method for diagnosis of VRL. Methods: Sixteen eyes in 12 patients with VRL, and 4 eyes in 4 patients with idiopathic uveitis presenting with vitreous opacity were enrolled in this study. Both undiluted vitreous and diluted fluids were isolated during micro-incision vitrectomy. Cell block specimens were prepared in 19 eyes from diluted fluid containing shredding vitreous. These specimens were then submitted for HE staining as well as immunocytological analyses with antibodies against the B-cell marker CD20, the T-cell marker CD3, and cell proliferation marker Ki67. Conventional smear cytology was applied in 14 eyes with VRL using undiluted vitreous samples. The diagnosis of VRL was made based on the results of cytology, concentrations of interleukin (IL)-10 and IL-6 in undiluted vitreous, and immunoglobulin heavy chain gene rearrangement analysis. Results: Atypical lymphoid cells were identified in 14 out of 15 cell block specimens of VRL (positive rate: 93.3 %), but in 5 out of 14 eyes in conventional smear cytology (positive rate: 35.7 %). Atypical lymphoid cells showed immunoreactivity for CD20 and Ki67. Seven cell block specimens were smear cytology-negative and cell block-positive. The cell block method showed no atypical lymphoid cells in any patient with idiopathic uveitis. Conclusions: Cell block specimens using diluted vitreous fluid demonstrated a high diagnostic sensitivity and a low pseudo-positive rate for the cytological diagnosis of VRL. The cell block method contributed to clear differentiation between VRL and idiopathic uveitis with vitreous opacity.背景：眼内リンパ腫（VRL）は視力・生命予後に影響を及ぼす疾患である。本研究ではVRLの診断における細胞塊（セルブロック）標本の有用性を検討することを目的とした。症例と方法：北海道大学病院眼科および他院を受診したVRL12例16眼、および硝子体混濁を呈した特発性ぶどう膜炎4例4眼を対象とした。小切開硝子体手術により、無希釈硝子体液および硝子体灌流液を採取した。19眼で、硝子体灌流液を用いたセルブロック標本を作製した。これらの標本を用いて特殊染色、およびB細胞マーカーである抗CD20抗体の免疫細胞化学的検討を行った。14眼では無希釈硝子体液を用いた塗抹細胞診を併せて行った。VRLの診断は、細胞診、無希釈硝子体液のIL-10, -6濃度、灌流液沈殿物から遺伝子再構成部位のモノクローナリティについて検討して行った。結果：VRLの15眼中14眼でセルブロック標本にて悪性リンパ腫細胞が検出された（陽性率：93.3％）。一方、塗抹細胞診では5眼で悪性細胞が検出された（陽性率：35.7％）。塗抹細胞診で陰性、セルブロックで陽性を示したIOL症例は7例8眼であった。特発性ぶどう膜炎では、悪性細胞が検出された症例はなかった（陽性率：0％）。VRL細胞はCD20陽性を示したが、特発性ぶどう膜炎ではCD20陽性細胞は検出されなかった。結語：硝子体灌流液を用いたセルブロック細胞診は、これまでの塗抹細胞診よりVRLの陽性率が高く、偽陽性も無かった。セルブロックは、VRLとぶどう膜炎との鑑別にも有用であることが示唆された。
  • Dong Y, Dong Z, Kase S, Ando R, Fukuhara J, Kinoshita S, Inafuku S, Tagawa Y, Ishizuka ET, Saito W, Murata M, Kanda A, Noda K, Ishida S
    International journal of ophthalmology 9 8 1100 - 1105 2016年 [査読有り][通常論文]
     
    AIM: To examine phosphorylation of alphaB-crystallin (p-αBC), a vascular endothelial growth factor (VEGF) chaperone, and immunohistochemically investigate relationship between p-αBC, VEGF and phosphorylated p38-mitogen-activated protein kinase (p-p38 MAPK) in the epiretinal membrane of human proliferative diabetic retinopathy (PDR). METHODS: Eleven epiretinal membranes of PDR surgically excised were included in this study. Two normal retinas were also collected from enucleation tissues due to choroidal melanoma. Paraformaldehyde-fixed, paraffin-embedded tissue sections were processed for immunohistochemistry with anti-p-αBC, VEGF, CD31, and p-p38 MAPK antibodies. RESULTS: Immunoreactivity for p-αBC was observed in all of the epiretinal membranes examined, where phosphorylation on serine (Ser) 59 showed strongest immunoreactivity in over 70% of the membranes. The immunolocalization of p-αBC was detected in the CD31-positive endothelial cells, and co-localized with VEGF and p-p38 MAPK in PDR membranes. Immunoreactivity for p-αBC, however, was undetectable in endothelial cells of the normal retinas, where p-p38 MAPK immunoreactivity was less marked than PDR membranes. CONCLUSION: Phosphorylation of αBC, in particular, phosphorylation on Ser59 by p-p38 MAPK may play a potential role as a molecular chaperon for VEGF in the pathogenesis of epiretinal membranes in PDR.
  • Kase S, Yokoi M, Ishida S, Kase M
    Biomedical reports 3 6 818 - 820 Spandidos Publications 2015年11月 [査読有り][通常論文]
     
    Measurements of interleukin (IL)-6 and -10 concentrations in the vitreous can be used to differentiate intraocular lymphoma (IOL) from uveitis. This is the first study reporting the IL-6 and -10 concentrations in the undiluted vitreous fluid and vitreous infusion fluid, which were simultaneously examined in the patients. A total of 2 females presented with intraocular inflammation, and underwent pars plana vitrectomy. Undiluted anterior vitreous and vitreous infusion fluid were collected simultaneously. IL concentrations were determined by enzyme-linked immunosorbent assay systems. Vitreous infusion fluid of 20 ml was eventually collected following completion of core vitrectomy in the two patients. IL-6 concentrations of the first patient were 513 and 106 pg/ml in the undiluted vitreous and the infusion fluid, respectively, while those of the second patient were 263 and 29 pg/ml. By contrast, IL-10 was under the detectable levels in all the fluids. The IL-10/-6 ratio was <1 in both fluids in the patients. Cytological examination revealed the presence of reactive inflammatory cells in the vitreous fluid. The two patients were eventually diagnosed with uveitis. Measurements of IL concentrations in the vitreous infusion fluid provided significant evidence on the differential diagnosis between IOL and uveitis, when considering how vitreous infusion fluid was diluted. The present study highlighted a novel application of cytokine analyses using the vitreous infusion fluid, which may contribute to the development of future translational researches on uveitis/IOL patients.
  • Satoru Kase, Toshiya Shinohara, Manabu Kase
    EXPERIMENTAL AND THERAPEUTIC MEDICINE 9 2 456 - 458 2015年02月 [査読有り][通常論文]
     
    The topical administration of rebamipide (Mucosta (R)), an antiulcer agent, clinically increases the mucin level of tear film. The aim of this study was to report the histological changes of goblet cells following the topical administration of rebamipide to a patient with nevus of the lacrimal caruncle. A 62-year-old male exhibited a pigmented nodule located in the lacrimal caruncle in the left eye. An excisional biopsy and subsequent surgical resection were conducted at the caruncle, prior to and three months after topical rebamipide administration. Histologically, a biopsy specimen revealed a pigmented nevus beneath the caruncle epithelium containing a few goblet cells [4 cells/high power field (HPF)]. A few nevus cells were present at the surgical margin. By contrast, the secondary resected specimen obtained three months after the initiation of topical rebamipide treatment revealed the epithelium and nevus, where numerous goblet cells were present (28 cells/HPF), and mucin-like substances were markedly secreted from the goblet cells. Topical rebamipide markedly increased the number of goblet cells and stimulated the secretion of mucin-like substances in the caruncular tissue of a human patient. These results suggest that topical rebamipide is useful in patients following surgery and/or biopsy to support tissue repair of the ocular surface.
  • Ishizuka ET, Kanda A, Kase S, Noda K, Ishida S
    Investigative ophthalmology & visual science 56 1 74 - 80 2014年12月 [査読有り][通常論文]
     
    PURPOSE: Extranodal marginal zone B-cell lymphoma (EMZL) is the most common subtype of conjunctival lymphoma, though its molecular mechanisms of pathogenesis are largely unknown. We attempted to explore the association of the renin-angiotensin system (RAS) and (pro)renin receptor ([P]RR) in the pathogenesis of conjunctival lymphoma. METHODS: Surgically removed conjunctiva EMZL samples were used for gene expression, and immunohistochemical and immunofluorescence analyses of (P)RR and RAS components. Human B-lymphoblast IM-9 cells were treated with prorenin or angiotensin II (Ang II), and gene expression levels were analyzed using real-time quantitative PCR (qPCR). In addition, immunofluorescence analysis of EMZL samples was used to evaluate the in vivo expression of those components. RESULTS: Gene expression and immunohistochemical analyses revealed the expression of RAS components, including (P)RR and angiotensin II type 1 receptor (AT1R), in EMZL tissues. Double-labeling analyses demonstrated that (P)RR and AT1R were detected in cells positive for CD20, a marker for B-cells, where they colocalized with prorenin and angiotensinogen, respectively. Prorenin stimulation of human B-lymphoblast IM-9 cells increased mRNA expression levels of fibroblast growth factor 2 (FGF2), while angiotensin II treatment upregulated the expression levels of basigin (BSG), matrix metallopeptidase (MMP)2, 9, and 14, which were abolished by (P)RR and AT1R blockades, respectively. Immunofluorescence analyses of clinical samples showed colocalizations of (P)RR and AT1R with the products of these upregulated genes. CONCLUSIONS: The present study suggests that activation of (P)RR and AT1R is associated with the pathogenesis of conjunctival EMZL by stimulating the production of FGF2 and MMPs.
  • Kase S, Noda M, Yoshikawa H, Yamamoto T, Ishijima K, Ishida S
    Ophthalmic plastic and reconstructive surgery 30 4 290 - 294 2014年07月 [査読有り][通常論文]
  • Kase S, Yoshikawa H, Nakajima Y, Noda M, Ishida S
    Oncology letters 7 6 1941 - 1943 Spandidos Publications 2014年06月 [査読有り][通常論文]
     
    Adenosquamous carcinoma (ASC) is a rare form of malignancy which consists of two types of cell, including squamous cells and glandular-like cells. The current report presents the first known case of ASC in the conjunctiva and analyzes the histological findings. A 76-year-old female presented with right eyelid swelling in 2001. A right conjunctival tumor was noted and a biopsy was performed. Histologically, the tumor was diagnosed as a squamous cell carcinoma. The patient underwent radiotherapy, but the tumor rapidly relapsed. Subsequently, the patient underwent orbital exenteration. Histologically, the conjunctival tissues had been replaced with invasive tumor cells. A number of tumor cells demonstrated squamous differentiation with a keratinizing tendency, while other tumor cells exhibited mucin-producing activity with glandular formation. The conjunctival tumor was diagnosed as an ASC. At the time of writing, the patient is well without local recurrence or distant metastases. ASC typically exhibits aggressive biological behavior, and is associated with worse prognosis than conventional adenocarcinoma. Therefore, complete surgical excision is considered a key treatment for ASC of the conjunctiva.
  • Kinoshita S, Kase S, Ando R, Dong Z, Fukuhara J, Dong Y, Inafuku S, Noda K, Noda M, Kanda A, Ishida S
    Investigative ophthalmology & visual science 55 6 3461 - 3467 2014年05月 [査読有り][通常論文]
  • Satoru Kase, Yasuo Suzuki, Toshiya Shinohara, Manabu Kase
    Orbit 33 3 217 - 219 2014年 [査読有り][通常論文]
     
    IgG4-related disease is characterized by elevated serum IgG4 and tissue infiltration by IgG4-positive plasma cells. We herein report a case of lacrimal sac diverticulitis with marked IgG4-positive plasma cell infiltration. An 89-year-old woman presenting with right lower eyelid mass. Imaging modalities demonstrated a cystic orbital mass located beneath the globe and adjacent to enlarged lacrimal sac. Serological tests showed high IgG4 and normal IgG levels, measuring 242 and 1603mg/dl, respectively. The orbital mass was surgically excised. Histologically, the excised tissue demonstrated marked inflammation with fibrosis surrounded by mononuclear epithelial cells. A variety of IgG and IgG4-positive plasma cells infiltrated the stroma. This patient was diagnosed as an IgG4-related lacrimal sac diverticulitis, based on current diagnostic criteria of IgG4-related disease. It is likely that IgG4-related inflammation occurs in a lacrimal sac diverticulum, which should be considered a differential diagnosis in inferior orbital tumors. © 2014 Informa Healthcare USA, Inc.
  • Saito W, Kase S, Fujiya A, Dong Z, Noda K, Ishida S
    Retina (Philadelphia, Pa.) 33 9 1959 - 1967 2013年10月 [査読有り][通常論文]
  • Kase S, Yamamoto T, Ishijima K, Noda M, Ishida S
    Modern rheumatology 23 5 1018 - 1021 2013年09月 [査読有り][通常論文]
  • Dong Z, Kase S, Ando R, Fukuhara J, Kinoshita S, Dong Y, Takashina S, Kanda A, Noda M, Noda K, Ishida S
    Anticancer research 33 9 3745 - 3751 2013年09月 [査読有り][通常論文]
  • Kase S, Namba K, Kitaichi N, Iwata D, Ohno S, Ishida S
    Japanese journal of ophthalmology 57 4 379 - 384 Springer 2013年07月 [査読有り][通常論文]
  • Kase S, Noda M, Ishijima K, Yamamoto T, Hatanaka K, Ishida S
    Anticancer research 33 6 2779 - 2783 2013年06月 [査読有り][通常論文]
  • Saito W, Kase S, Ohguro H, Ishida S
    Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 251 5 1447 - 1449 Springer 2013年05月 [査読有り][通常論文]
  • Nao Saito, Naoya Yoshioka, Riichiro Abe, Hongjiang Qiao, Yasuyuki Fujita, Daichi Hoshina, Asuka Suto, Satoru Kase, Nobuyoshi Kitaichi, Michitaka Ozaki, Hiroshi Shimizu
    JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 131 2 434 - + 2013年02月 [査読有り][通常論文]
     
    Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening cutaneous reactions caused by drugs or infections and exhibiting widespread epidermal necrosis. Currently, there is no animal model that reproduces SJS/TEN symptoms. Objective: We sought to develop a novel mouse model of SJS/TEN by using PBMCs and skin from patients who had recovered from SJS/TEN. Methods: For our mouse model, patients' PBMCs were injected intravenously into immunocompromised NOD/Shi-scid, IL-2R gamma(null) (NOG) mice, followed by oral administration of a causative drug. Subsequently, to replace human skin, unaffected skin specimens obtained from patients who had recovered from SJS/TEN were grafted onto NOG mice, after which patient-derived PBMCs and the causative drug were applied. Results: Mice injected with PBMCs from patients with SJS/TEN and given the causative drug showed marked conjunctival congestion and numerous cell death of conjunctival epithelium, whereas there were no symptoms in mice injected with PBMCs from patients with ordinary drug skin reactions. CD8(+) T lymphocyte-depleted PBMCs from patients with SJS/TEN did not elicit these symptoms. In addition, skin-grafted mice showed darkening of the skin-grafted areas. Cleaved caspase-3 staining showed that dead keratinocytes were more numerous in the skin-grafted mice than in the healthy control animals. Conclusion: We have established a novel human-oriented SJS/TEN mouse model and proved the importance of CD8(+) T lymphocytes in SJS/TEN pathogenesis. The mouse model promises to promote diagnostic and therapeutic approaches. (J Allergy Clin Immunol 2013;131:434-41.)
  • Fukuhara J, Kase S, Ohashi T, Ando R, Dong Z, Noda K, Ohguchi T, Kanda A, Ishida S
    Histochemistry and cell biology 139 2 381 - 389 2 2013年02月 [査読有り][通常論文]
     
    Purpose: Vascular endothelial growth factor C (VEGF-C) and its receptor VEGFR-3 mediate lymphangiogenesis. In this study, we analyzed the expression of VEGF-C and VEGFR-3 as well as lymphatic vessels in the pterygium and normal conjunctiva of humans. Methods: Fifteen primary nasal pterygia and three normal bulbar conjunctivas, surgically removed, were examined in this study. The lymphatic vessel density (LVD) and blood vessel density (BVD) were determined by the immunolabeling of D2-40 and CD31, markers for lymphatic and blood vessels, respectively. VEGF-C and VEGFR-3 expression in pterygial and conjunctival tissue proteins was detected by Western blotting. Expressions of VEGF-C and VEGFR-3 were evaluated using immunohistochemistry. Results: The LVD was significantly higher in the pterygium than normal conjunctiva (p<0.05). Western blot demonstrated high-level expression of VEGF-C and VEGFR-3 in the pterygium compared with normal conjunctiva. VEGF-C immunoreactivity was detected in the cytoplasm of pterygial and normal conjunctival epithelial cells. The number of VEGF-C-immunopositive cells in pterygial epithelial cells was significantly higher than in normal conjunctival cells (p<0.05). VEGFR-3 immunoreactivity was localized in the D2-40-positive lymphatic endothelial cells. Conclusions: The present findings suggest the potential role of VEGF-C in the pathogenesis and development of a pterygium through lymphangiogenesis and the VEGF-C/VEGFR-3 pathway as a novel therapeutic target for the human pterygium.
  • Lennikov A, Kitaichi N, Kase S, Noda K, Horie Y, Nakai A, Ohno S, Ishida S
    International journal of molecular sciences 14 1 2175 - 2189 MDPI 2013年01月 [査読有り][通常論文]
     
    Acute ultraviolet (UV) B exposure causes photokeratitis and induces apoptosis in corneal cells. Geranylgeranylacetone (GGA) is an acyclic polyisoprenoid that induces expression of heat shock protein (HSP) 70, a soluble intracellular chaperone protein expressed in various tissues, protecting cells against stress conditions. We examined whether induction of HSP70 has therapeutic effects on UV-photokeratitis in mice. C57 BL/6 mice were divided into four groups, GGA-treated (500 mg/kg/mouse) and UVB-exposed (400 mJ/cm2), GGA-untreated UVB-exposed (400 mJ/cm2), GGA-treated (500 mg/kg/mouse) but not exposed and naive controls. Eyeballs were collected 24 h after irradiation, and corneas were stained with hematoxylin and eosin (H&E) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). HSP70, reactive oxygen species (ROS) production, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and protein kinase B (Akt) expression were also evaluated. Irradiated corneal epithelium was significantly thicker in the eyes of mice treated with GGA compared with those given the vehicle alone (p < 0.01). Significantly fewer TUNEL-positive cells were observed in the eyes of GGA-treated mice than controls after irradiation (p < 0.01). Corneal HSP70 levels were significantly elevated in corneas of mice treated with GGA (p < 0.05). ROS signal was not affected by GGA. NF-κB activation was reduced but phospho-(Ser/Ther) Akt substrate expression was increased in corneas after irradiation when treated with GGA. GGA-treatment induced HSP70 expression and ameliorated UV-induced corneal damage through the reduced NF-κB activation and possibly increased Akt phosphorilation.
  • Terasaki H, Kase S, Shirasawa M, Otsuka H, Hisatomi T, Sonoda S, Ishida S, Ishibashi T, Sakamoto T
    PloS one 8 7 e69994  2013年 [査読有り][通常論文]
     
    Asymmetrical secretion of vascular endothelial growth factor (VEGF) by retinal pigment epithelial (RPE) cells in situ is critical for maintaining the homeostasis of the retina and choroid. VEGF is also involved in the development and progression of age-related macular degeneration (AMD). We studied the effect of tumor necrosis factor-α (TNF-α) on the secretion of VEGF in polarized and non-polarized RPE cells (P-RPE cells and N-RPE cells, respectively) in culture and in situ in rats. A subretinal injection of TNF-α caused a decrease in VEGF expression and choroidal atrophy. Porcine RPE cells were seeded on Transwell™ filters, and their maturation and polarization were confirmed by the asymmetrical VEGF secretion and trans electrical resistance. Exposure to TNF-α decreased the VEGF secretion in P-RPE cells but increased it in N-RPE cells in culture. TNF-α inactivated JNK in P-RPE cells but activated it in N-RPE cells, and TNF-α activated NF-κB in P-RPE cells but not in N-RPE cells. Inhibition of NF-κB activated JNK in both types of RPE cells indicating crosstalk between JNK and NF-κB. TNF-α induced the inhibitory effects of NF-κB on JNK in P-RPE cells because NF-κB is continuously inactivated. In N-RPE cells, however, it was not evident because NF-κB was already activated. The basic activation pattern of JNK and NF-κB and their crosstalk led to opposing responses of RPE cells to TNF-α. These results suggest that VEGF secretion under inflammatory conditions depends on cellular polarization, and the TNF-α-induced VEGF down-regulation may result in choroidal atrophy in polarized physiological RPE cells. TNF-α-induced VEGF up-regulation may cause neovascularization by non-polarized or non-physiological RPE cells.
  • Kase S, Rao NA, Yoshikawa H, Fukuhara J, Noda K, Kanda A, Ishida S
    Investigative ophthalmology & visual science 54 1 57 - 62 1 2013年01月 [査読有り][通常論文]
  • Fukuhara J, Kase S, Noda M, Ishijima K, Yamamoto T, Ishida S
    World journal of surgical oncology 10 194 - 194 BioMed Central 2012年09月 [査読有り][通常論文]
     
    Extra nodal marginal zone B-cell lymphoma (EMZL) of the conjunctiva typically arises in the marginal zone of mucosa-associated lymphoid tissue. The pathogenesis of conjunctival EMZL remains unknown. We describe an unusual case of EMZL arising from reactive lymphoid hyperplasia (RLH) of the conjunctiva. A 35-year-old woman had fleshy salmon-pink conjunctival tumors in both eyes, oculus uterque (OU). Specimens from conjunctival tumors in the right eye, oculus dexter (OD), revealed a collection of small lymphoid cells in the stroma. Immunohistochemically, immunoglobulin (Ig) light chain restriction was not detected. In contrast, diffuse atypical lymphoid cell infiltration was noted in the left eye, oculus sinister (OS), and positive for CD20, a marker for B cells OS. The tumors were histologically diagnosed as RLH OD, and EMZL OS. PCR analysis detected IgH gene rearrangement in the joining region (JH) region OU. After 11 months, a re-biopsy specimen demonstrated EMZL based on compatible pathological and genetic findings OD, arising from RLH. This case suggests that even if the diagnosis of the conjunctival lymphoproliferative lesions is histologically benign, confirmation of the B-cell clonality by checking IgH gene rearrangement should be useful to predict the incidence of malignancy.
  • Iwata D, Namba K, Mizuuchi K, Kitaichi N, Kase S, Takemoto Y, Ohno S, Ishida S
    Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 250 7 1081 - 1087 Springer Berlin / Heidelberg 2012年07月 [査読有り][通常論文]
     
    Background: Infliximab, an anti-TNF-α monoclonal antibody, administered to Behçet's disease (BD) patients in Japan with refractory intraocular inflammation, has shown excellent clinical results. However, some patients demonstrate a decreased response to infliximab during the course of the treatment. In the present study, we investigated the correlation between this reduced therapeutic effect and elevation of the serum antinuclear antibody (ANA) titers in patients with BD who were undergoing infliximab therapy. Methods: Seventeen patients (14 males and 3 females) with uveitis in BD who were undergoing treatment with infliximab for 2 years or longer were enrolled. Their blood test results and clinical histories were obtained from medical records. Results: One patient (5.9%) was ANA-positive prior to the initiation of infliximab, and 11 patients (64.7%) developed positive ANA during the therapy. The appearance of ANA was observed 6 months after the initiation of the infliximab therapy, and its titres gradually increased. None of the patients showed lupus symptoms. Five patients (29.4%) have suffered from ocular inflammatory attacks since 6th month from the initiation of infliximab treatment and all of them were ANA-positive. In contrast, 4 patients (23.5%) who were ANA-negative experienced no ocular attacks during the follow-up period. Conclusions: Here we report the positive conversion and subsequent elevation of serum ANA titres in some patients with BD after the initiation of infliximab therapy. Since all recurrences of uveitis were shown only in the ANA-positive patients, serum ANA titre may be a helpful biomarker for predicting the recurrence of ocular attacks in BD patients treated with anti-TNF-α antibody therapies.
  • Dong Z, Kase S, Ando R, Fukuhara J, Saito W, Kanda A, Murata M, Noda K, Ishida S
    Retina (Philadelphia, Pa.) 32 6 1190 - 1196 6 2012年06月 [査読有り][通常論文]
     
    PURPOSE: To examine the expression of alphaB-crystallin and its colocalization with vascular endothelial growth factor in the epiretinal membrane of human proliferative diabetic retinopathy. METHODS: Ten epiretinal membranes of proliferative diabetic retinopathy and three normal retinas surgically excised were included in this study. Paraformaldehyde-fixed, paraffin-embedded tissue sections were processed for immunohistochemistry with alphaB-crystallin, vascular endothelial growth factor, and CD31 antibodies. RESULTS: AlphaB-crystallin was expressed in all epiretinal membranes examined. The immunolocalization of alphaB-crystallin was detected in the cytoplasm of CD31-positive endothelial cells, but not in normal retinal blood vessels. Furthermore, alphaB-crystallin immunoreactivity was colocalized in vascular endothelial growth factor-positive endothelial cells in proliferative diabetic retinopathy membranes. CONCLUSION: AlphaB-crystallin was expressed in proliferative diabetic retinopathy membranes, and colocalized with vascular endothelial growth factor-positive neovessels. AlphaB-crystallin may play a potential role in the pathogenesis of epiretinal membranes in proliferative diabetic retinopathy, together with vascular endothelial growth factor.
  • Murata M, Noda K, Fukuhara J, Kanda A, Kase S, Saito W, Ozawa Y, Mochizuki S, Kimura S, Mashima Y, Okada Y, Ishida S
    Investigative ophthalmology & visual science 53 7 4055 - 4062 7 2012年06月 [査読有り][通常論文]
     
    PURPOSE: Vascular adhesion protein (VAP)-1, a multifunctional molecule with adhesive and enzymatic properties, is expressed at the surface of vascular endothelial cells of mammals. It also exists as a soluble form (sVAP-1), which is implicated in oxidative stress via its enzymatic activity. This study explores a link between increased level of sVAP-1 and oxidative stress in proliferative diabetic retinopathy (PDR) with a focus on mechanistic components to form sVAP-1 by shedding from retinal endothelial cells. METHODS: Protein levels of sVAP-1 and N epsilon-(hexanoyl)lysine (HEL), an oxidative stress marker, in the vitreous samples from patients with PDR or non-PDR were measured by ELISA. The mechanism of VAP-1 shedding under diabetic condition, exposure to high glucose and/or inflammatory cytokines, was explored using cultured retinal capillary endothelial cells. RESULTS: Protein level of sVAP-1 was increased and correlated with HEL in the vitreous fluid of patients with PDR. Retinal capillary endothelial cells released sVAP-1 when stimulated with high glucose or inflammatory cytokines, such as TNF-α and IL-1β in vitro. Furthermore, matrix metalloproteinase-2 and -9, type IV collagenases, were the key molecules to mediate the protein cleavage of VAP-1 from retinal capillary endothelial cells. CONCLUSIONS: Our data for the first time provide evidence on the link between sVAP-1 and type IV collagenases in the pathogenesis of PDR.
  • Kase S, Namba K, Jin XH, Kubota KC, Ishida S
    Ophthalmology 119 5 1083 - 1084 2012年05月 [査読有り][通常論文]
  • 眼窩IgG4関連疾患を背景に発生したと考えたIgG4陽性形質細胞を伴う節外性濾胞辺縁帯B細胞性リンパ腫の1例
    久保田 佳奈子, ヘールナンデス 真子, 藤田 裕美, 山田 洋介, 加瀬 諭, 畑中 豊, 高桑 恵美, 三橋 智子, 松野 吉宏
    日本病理学会会誌 101 1 381 - 381 (一社)日本病理学会 2012年03月 [査読有り][通常論文]
  • Kase S, Meghpara BB, Ishida S, Rao NA
    Molecular medicine reports 5 2 395 - 399 2012年02月 [査読有り][通常論文]
  • Hase K, Kase S, Noda M, Ohashi T, Shinkuma S, Ishida S
    Case reports in dermatology 4 1 37 - 40 1 2012年01月 [査読有り][通常論文]
     
    Cilia are normally found at the eyelid margin, while ectopic cilia are one or more lash follicles appearing in an abnormal position within the eyelid. We herein report two cases of cilia located in the palpebral conjunctiva. A 31-year-old female and a 46-year-old male presented with ectopic cilia in the superior palpebral conjunctiva. Histopathological study of the excised ectopic cilia and related lesions showed the cilia-related lesion to be located in the epithelial pit that contains goblet cells, which is consistent with the crypts of Henle. The hair follicle was surrounded by granulation tissue, while a dermal papilla and a hair matrix, which are known to produce hair follicles, did not exist in the excised tissue. While anterior ectopic cilia are congenital, ectopic cilia in the palpebral conjunctiva may be acquired, and these aberrant cilia are associated with crypts of Henle and chronic inflammation.
  • Hashimoto Y, Kase S, Saito W, Ishida S
    The open ophthalmology journal 6 125 - 128 2012年 [査読有り][通常論文]
  • Fukuhara J, Kase S, Noda K, Murata M, Noda M, Ando R, Dong Z, Kanda A, Ishida S
    Ophthalmic research 48 1 33 - 37 1 2012年 [査読有り][通常論文]
     
    OBJECTIVE: We analyzed the expression and immunolocalization of vascular adhesion protein (VAP)-1 in conjunctival tumors and normal conjunctival tissue of humans. METHODS: Nine conjunctival tumors, including pyogenic granuloma and extranodal marginal zone B-cell lymphoma (EMZL), and 2 normal conjunctivas were analyzed by immunohistochemistry for VAP-1 and CD31 expression. RESULTS: Immunoreactivity for VAP-1 was detected in the lumen of microvessels in pyogenic granuloma and in EMZLs. In contrast, normal bulbar conjunctival tissues demonstrated weak cytoplasmic immunoreactivity for VAP-1 in the blood vessels. CONCLUSIONS: The immunolocalization of VAP-1 varied in the histopathology of the conjunctiva, involving the pathology of inflammatory conjunctival disorders.
  • Ishijima K, Kase S, Noda M, Ishida S
    European journal of ophthalmology 21 6 837 - 840 2011年11月 [査読有り][通常論文]
  • Kase S, Ishida S, Rao NA
    International journal of molecular medicine 28 4 505 - 511 2011年10月 [査読有り][通常論文]
  • Fukuhara J, Kase S, Noda M, Ishijima K, Ishida S
    Oncology letters 2 3 489 - 491 Spandidos 2011年05月 [査読有り][通常論文]
     
    A 66-year-old female had suffered from proptosis in the left eye (OS) and double vision for 1 month due to abnormality of the superior rectus muscle. Visual acuity was noted as 20/20 in both eyes (OU). Eye movement showed limited OS supraduction. Magnetic resonance imaging revealed an indistinct mass in the orbit involving the superior rectus muscle. A biopsy specimen of the orbital tumor led to the histological diagnosis of extranodal marginal zone B-cell lymphoma. Radiotherapy with a total dosage of 30 Gy was administered, which subsequently resolved the tumor. However, the supraduction limitation of ocular movement remained unchanged. Supraduction limitation is due to muscular contraction disorder of the superior rectus muscle, caused by direct lymphoma cell invasion.
  • Fukuhara J, Kase S, Ishijima K, Noda M, Ishida S
    Ophthalmology 118 2 423.e1 - 2 2011年02月 [査読有り][通常論文]
  • Kase S, Yoshida K, Suzuki S, Ohshima K, Ohno S, Ishida S
    Clinical ophthalmology (Auckland, N.Z.) 5 861 - 863 Dove Medical Press 2011年 [査読有り][通常論文]
     
    We report herein an unusual case of diffuse infiltrating retinoblastoma involving the brain, which caused a patient's death 27 months after enucleation. An eight-year-old boy complained of blurred vision in his right eye (OD) in October 2006. Funduscopic examination showed optic disc swelling, dense whitish vitreous opacity, and an orange-colored subretinalelevated lesion adjacent to the optic disc. Fluorescein angiography revealed hyperfluorescencein the peripapillary region at an early-phase OD. Because the size of the subretinal lesion andvitreous opacity gradually increased, he was referred to us. His visual acuity was 20/1000 OD on June 20, 2007. Slit-lamp biomicroscopy showed a dense anterior vitreous opacity. Ophthalmoscopically, the subretinal orange-colored area spread out until reaching the midperipheral region. A B-mode sonogram and computed tomography showed a thick homogeneous lesion without calcification. Gadolinium-enhanced magnetic resonance imaging showed a markedly enhanced appearance of the underlying posterior retina. Enucleation of the right eye was performed nine months after the initial presentation. Histopathology demonstrated retinaldetachment and a huge choroidal mass invading the optic nerve head. The tumor was consistent with diffuse infiltrating retinoblastoma. The patient died due to brain involvement 27 months after enucleation. Ophthalmologists should be aware that diffuse infiltrating retinoblastoma may show an unfavorable course if its diagnosis is delayed.
  • Ando R, Kase S, Ohashi T, Dong Z, Fukuhara J, Kanda A, Murata M, Noda K, Kitaichi N, Ishida S
    Molecular vision 17 63 - 69 Molecular vision 2011年01月 [査読有り][通常論文]
     
    Purpose: A pterygium shows tumor-like characteristics, such as proliferation, invasion, and epithelial–mesenchymal transition (EMT). Previous reports suggest that tissue factor (TF) expression is closely related to the EMT of tumor cells, and subsequent tumor development. In this study, we analyzed the expression and immunolocalization of TF in pterygial and normal conjunctival tissues of humans. Methods: Eight pterygia and three normal bulbar conjunctivas, surgically removed, were used in this study. Formalinfixed, paraffin-embedded tissues were submitted for immunohistochemical analysis with anti-TF antibody. Double staining immunohistochemistry was performed to assess TF and alpha-smooth muscle actin (α-SMA) or epidermal growth factor receptor (EGFR) expression in the pterygia. Results: Immunoreactivity for TF was detected in all pterygial tissues examined. TF immunoreactivity was localized in the cytoplasm of basal, suprabasal, and superficial epithelial cells. The number of TF-immunopositive cells in pterygialepithelial cells was significantly higher than in normal conjunctival epithelial cells (p<0.001). TF immunoreactivity was detected in α-SMA-positive or -negative pterygial epithelial cells. EGFR immunoreactivity was detected in pterygial epithelium, which was colocalized with TF. Conclusions: These results suggest that TF plays a potential role in the pathogenesis and development of a pterygium, and that TF expression might be involved through EMT-dependent and -independent pathways.
  • Wataru Saito, Satoru Kase, Kazuhiro Ohgami, Shohei Mori, Shigeaki Ohno
    ACTA OPHTHALMOLOGICA 88 3 377 - 380 2010年05月 [査読有り][通常論文]
     
    Purpose: To describe two patients with macular oedema secondary to tuberous sclerosis complex (TSC) who were treated with intravitreal bevacizumab injection. Methods: Interventional case reports. Bevacizumab 1.25 mg was injected into the vitreous of two patients with TSC-associated macular oedema / exudative retinal detachment. Vascular endothelial growth factor (VEGF) concentration in the vitreous fluid was measured by enzyme-linked immunosorbent assay (ELISA) in one of these patients. Results: Patient 1: a 22-year-old woman with TSC was diagnosed as having multiple retinal hamartomas in both eyes. Eleven years later, the patient developed macular oedema with epiretinal membrane formation in the right eye. The patient underwent pars-plana vitrectomy with retinal photocoagulation for retinal tumours. VEGF concentration in the vitreous fluid was high compared to that in patients without retinal vascular diseases. Recurrent macular oedema disappeared by intravitreal injection of bevacizumab. Patient 2: a 32-year-old woman with TSC-associated retinal hamartoma, temporally showing macular exudative retinal detachment, developed neovascularization originated from the tumour. By intravitreal bevacizumab injection, the tumour size reduced markedly with regression of neovascularization. Conclusion: These results suggest that VEGF derived from retinal hamartomas causes macular oedema associated with TSC. Intravitreal injections of bevacizumab may be a useful therapeutic option for macular oedema secondary to TSC.
  • Kase S, Saito W, Ohno S, Ishida S
    Retina (Philadelphia, Pa.) 30 5 719 - 723 2010年05月 [査読有り][通常論文]
  • Kase S, Ishijima K, Ishida S, Rao NA
    Ophthalmology 117 3 637.e1 - 2 2010年03月 [査読有り][通常論文]
  • N. Saito, T. Yanagi, M. Akiyama, H. Y. Lin, S. Kasai, Y. Fujita, N. Yamane, D. Inokuma, S. Kase, K. Ono, H. Minakawa, H. Shimizu
    DERMATOLOGY 221 3 211 - 215 2010年 [査読有り][通常論文]
     
    Pyoderma gangrenosum (PG) of the eyelid is extremely rare, and its proper management is essential for the preservation of visual function. Here, we report 2 cases of PG of the eyelid with intraorbital involvement. In both cases, the skin and intraorbital lesions improved after systemic immunosuppressive therapies; however, corneal perforation occurred in 1 case. In order to assess the clinical features of PG of the eyelid and to obtain clues for optimal treatment, we reviewed 15 well-documented cases in the literature, including the present cases. Corneal perforation occurred in 4 cases and defective ocular motility in 1 case. Three patients eventually underwent enucleation of the affected eye. Our cases and the literature review clearly indicate that MRI is a powerful tool for evaluating the extent of extracutaneous PG lesions around the eye and that early diagnosis and immediate immunosuppressive therapy are crucial for the preservation of visual acuity. Copyright (C) 2010 S. Karger AG, Basel
  • Kase S, Saito W, Ohno S, Ishida S
    Investigative ophthalmology & visual science 50 12 5909 - 5912 2009年12月 [査読有り][通常論文]
  • Kazuhiko Yoshida, Yukiko Tomioka, Satoru Kase, Masami Morimatsu, Kyoko Shinya, Shigeaki Ohno, Etsuro Ono
    GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY 246 4 543 - 549 2008年04月 [査読有り][通常論文]
     
    Background Nectins are Ca2+-independent immunoglobulin (Ig)-like cell-cell-adhesion molecules. We have generated transgenic mice expressing a series of soluble forms of nectin-1, and investigated special effects of each soluble form of nectin-1 in vivo. In the course of generating transgenic mice expressing a soluble form of nectin-1 consisting of the first Ig-like domain of nectin-1 and the Fc portion of human IgG1 (PHveC-VhIg), we found that all of the transgenic founder mice showed a microphthalmia. The purpose of this study is to examine functions of the extracellular domains of nectin-1 in eye development using transgenic technology. Methods Eyes of four different transgenic mouse lines expressing each soluble form of nectin-1 were analyzed histologically. Tissue sections were processed with hematoxylin-eosin staining and indirect immunoperoxidase technique. Results All of five transgenic mouse founders expressing PHveC-VhIg, and of three lines expressing PHveC-VpIg made of the first Ig-like domain fused to porcine Fc portions at 5 weeks showed a microphthalmia, but not all of the transgenic mouse lines expressing PHveCIg or PHveCpIg made of the entire ectodomain fused to human or porcine Fc portions. In the abnormal eyes, the vitreous body was almost absent. In PHveC-VhIg-expressing mice at postnatal day 6, each vitreous space was very small. In the neonatal transgenic mice, the vitreous body was almost the same as that of control mice, and PHveC-VhIg was expressed in the optic nerve, conjunctival epithelium, ciliary body, corneal and lens epithelium. At this stage, nectin-1, -3 and -4 were stained in the optic nerve of control mice as well as in that of the transgenic mice. Nectin-1 is faintly stained in the epithelium of the cornea and lens epithelium, but not in the ciliary body. Conclusion Soluble forms of the first Ig-like domain of nectin-1 (PHveC-VhIg and PHveC-VpIg), but not those of the entire ectodomain (PHveCIg and PHveCpIg), lead to microphthalmia and lack of vitreous body in the transgenic mice.
  • Satoru Kase, Mitsuhiko Osaki, Xue-Hai Jin, Kazuhiro Ohgami, Kazuhiko Yoshida, Wataru Saito, Shuji Takahashi, Katsuya Nakanishi, Hisao Ito, Shigeaki Ohno
    INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 20 5 699 - 702 2007年11月 [査読有り][通常論文]
     
    Erythropoietin (Epo) induces physiological activities such as cell proliferation, migration, and angiogenesis in Epo receptor (EpoR)-expressing vascular endothelial and tumor cells. Recently, it has been demonstrated that growth factor-independent proliferation is frequently observed during the cell transformation process. Pterygium is a fibrovascular proliferating tissue that includes transformed cells. The aim of this study was to examine the localization of Epo and EpoR proteins in human pterygial tissues. Eleven samples including nine pterygia and two normal bulbar conjunctivas, which were surgically excised, were studied. Formalin-fixed, paraffin-embedded tissue sections were constructed and then were examined by immunohistochemistry with anti-Epo and EpoR antibodies. Cytoplasmic immunoreactivity for EpoR was heterogeneously detected in basal and suprabasal cells of the pterygium epithelium. In the pterygium stroma, a variety of endothelial cells forming vascular cavities showed cytolasmic immunoreactivity for EpoR. In normal conjunctival epithelium, a few basal cells showed a weak homogeneous immunoreactivity for EpoR in the cytoplasm. The number of EpoR-expressing epithelial cells was much higher in the pterygiurn compared to the normal conjunctiva. EpoR expression was marginally detected in stromal microvessels of the normal conjunctiva. Immunoreactivity for Epo was not noted in pterygiurn epithelium and stroma, and in normal conjunctiva. These results suggest that the Epo-independent EpoR-signaling pathway plays a potential role in cell proliferation and angiogenesis in human pterygium.
  • Satoru Kase, Wataru Saito, Kazuhiro Ohgami, Kazuhiko Yoshida, Naoki Furudate, Akari Saito, Masahiko Yokoi, Manabu Kase, Shigeaki Ohno
    BRITISH JOURNAL OF OPHTHALMOLOGY 91 10 2007年10月 [査読有り][通常論文]
     
    Purpose: It is widely accepted that intravitreous levels of erythropoietin ( Epo) are elevated in patients with ischaemic retinal diseases such as proliferative diabetic retinopathy ( PDR). The aim of this study was to examine the expression of Epo and the Epo receptor ( EpoR) in epiretinal membranes with and without diabetes. Methods: Eighteen epiretinal membranes ( PDR ( n = 10), idiopathic epiretinal membranes ( IERMs) without diabetes ( n = 4) and inner limiting membranes ( ILMs) ( n = 4)) were obtained during pars plana vitrectomy. Formalin-fixed and paraffin-embedded tissues were examined by immunohistochemistry with anti-Epo and EpoR antibodies. Results: The histopathological findings demonstrated that PDR membranes consisted of a variety of endothelial cells forming a microvascular cavity with red blood cells and non-vascular stromal mononuclear cells. Membranous and cytoplasmic immunoreactivity for EpoR was strongly detected in endothelial cells and stromal cells in all PDR patients. Although microvessels were not observed in IERMs and ILMs, immunoreactivity for EpoR was noted in the cellular component of IERMs, and was weakly detected in ILMs. Epo was not expressed in any membrane. Conclusion: EpoR was strongly expressed in microvessels of all PDR membranes. The in vivo evidence in this study suggests that Epo in the vitreous binds to EpoR in PDR membranes, which subsequently leads to the proliferation of new retinal vessels. EpoR immunoreactivity in non-vascular stromal cells in PDR membranes, and IERMs and ILMs might be indirectly correlated with ischaemia.
  • Jin Xue-Hai, Ohgami Kazuhiro, Shiratori Kenji, Koyama Yoshikazu, Yoshida Kazuhiko, Kase Satoru, Ohno Shigeaki
    British Journal of Ophthalmology 91 3 369 - 371 BMJ Publishing Group 2007年03月 
    Aims: Hydrogen peroxide (H2O2) is the major oxidant involved in cataract formation. Lens epithelial cells have been suggested to be the first site of oxidative damage. The authors investigated the relationship between H2O2-induced cytotoxicity and activation of nuclear factor kappa B (NF-B) in human lens epithelial (HLE) cells. Methods: HLE B-3 cells were stimulated by various concentrations of H2O2 in the presence or absence of pyrrolidine dithiocarbamate (PDTC), a potent inhibitor of NF-B. H2O2-induced cytotoxicity was measured by lactate dehydrogenase cytotoxicity assay. Translocation of NF-B was examined by Western blot and immunocytochemistry using anti-p65 antibody. Results: H2O2-induced cytotoxicity increased in a concentration-dependent manner. PDTC treatment significantly suppressed the cytotoxicity induced by H2O2. After stimulated with H2O2, NF-B was found translocated from cytoplasm into the nuclei. PDTC treatment also inhibited the translocation of NF-B. Conclusions: NF-B signal pathway may be important in the development of H2O2-induced damage in HLE cells that is involved in cataractogenesis.
  • Satoru Kase, Kenichi Namba, Yukihiro Horie, Satoshi Kotake, Shigeaki Ohno
    Journal of Medical Investigation 54 3-4 350 - 353 2007年 [査読有り][通常論文]
     
    HLA-B27 associated uveitis is characterized by recurrent alternating acute unilateral attacks of intraocular inflammation in the anterior chamber. The aim of this study was to report an unusual case of repeated exacerbations with vitreous hemorrhage in HLA-B27 associated uveitis. Thirty four-year-old man was diagnosed as HLA-B27 associated uveitis in his right eye. He showed repeated exacerbation of ocular inflammation with retinal vein dilation and small retinal hemorrhage following vitreous hemorrhage. Fluorescein fundus angiography a week before the appearance of vitreous hemorrhage showed no neovascularization. Oral prednisolone administration was started from 40 mg/day with gradual tapering. About 3 weeks after the onset, most of the vitreous hemorrhage disappeared and visual acuity was improved to 20/20. Through the decreased vitreous hemorrhage, Weiss ring was detected later. The vitreous hemorrhage found in this patient is a severe exacerbation, and might be a consequence of the vitritis that leads to posterior vitreous detachment.
  • Yukihiro Horie, Yuko Takemoto, Akiko Miyazaki, Kenichi Namba, Satoru Kase, Kazuhiko Yoshida, Masao Ota, Yukiko Hasumi, Hidetoshi Inoko, Nobuhisa Mizuki, Shigeaki Ohno
    Molecular vision 12 12 1601 - 5 2006年12月20日 [査読有り][通常論文]
     
    PURPOSE: The aim of the present study was to examine the genetic background of Vogt-Koyanagi-Harada (VKH) disease in a Japanese population by analyzing the tyrosinase gene family (TYR, TYRP1, and dopachrome tautomerase (DCT)). METHODS: 87 VKH patients and 122 healthy controls were genotyped using seven microsatellite markers on the candidate loci. We analyzed microsatellite (MS) polymorphisms at regions within tyrosinase gene family loci. In addition, the haplotype frequencies were also estimated and statistical analysis was performed. HLA-DRB1 genotyping was performed by the PCR-restriction fragment length polymorphism (RFLP) method. RESULTS: No significant evidence for an association was found. HLA-DRB1*0405 showed a highly significant association with VKH disease compared with the healthy controls (Pc=0.000000079), as expected. CONCLUSIONS: We concluded that there is no genetic susceptibility or increased risk attributed to the tyrosinase gene family. Our results suggest the need for further genetic study and encourage a search for novel genetic loci and predisposing genes in order to elucidate the genetic mechanisms underlying VKH disease.
  • Satoru Kase, Kazuhiko Yoshida, Xue-Hai Jin, Yoshikazu Koyama, Nobuyoshi Kitaichi, Kazuhiro Ohgami, Kenji Shiratori, Iliyana Ilieva, Shigeaki Ohno
    International journal of molecular medicine 18 6 1187 - 91 2006年12月 [査読有り][通常論文]
     
    Opacification of the posterior capsule depends on replication of the residual lens epithelial cells lining the capsule. However, the mechanisms in the regulation of lens cell proliferation have not been determined. The purpose of this study is to examine the expression of p27(KIP1), a cyclin-dependent kinase inhibitor, and its phosphorylation, and cyclin D1 in lens epithelial cells after extraction of fiber cells. C57Bl6 mice (12 weeks old) were anesthetized, and the lens fiber cells were surgically extracted. Eyeballs were collected and fixed at 15 min and 24 h after extraction with and without injection of a specific phosphorylated extracellular signal-regulated kinase (pERK) 1/2 inhibitor (PD98059) to the anterior chamber. Collected tissues were analyzed using immunohistochemistry with anti-p27(KIP1), anti-phosphorylated p27(KIP1) on serine 10 (s10-phospho-p27) and cyclin D1 antibodies. Human lens epithelial cells were cultured, and then were treated with and without 40 ng/ml human recombinant basic fibroblast growth factor (bFGF), which was analyzed by Western blot analysis. In the untreated lens, p27(KIP1) was not phosphorylated in the lens epithelial cells, although p27(KIP1)-positive nuclei were detected in the lens cells of the equatorial region. Immunoreactivity for cyclin D1 was hardly detected in the lens. Nuclear immunoreactivity for p27(KIP1) and s10-phospho-p27 was observed in several lens cells of the equatorial region 15 min after extraction of fiber cells. Western blotting demonstrated that the p27(KIP1) phosphorylation form was upregulated 15 min after bFGF treatment in cultured lens epithelial cells. Many cyclin D1-positive nuclei were noted 24 h after the surgery. p27(KIP1) phosphorylation and cyclin D1 induction were inhibited by PD98059. s10-phospho-p27 and p27(KIP1) immunoreactivity was undetected in the lens cells 24 h after the extraction of fiber cells. It is possible that the phosphorylation of p27(KIP1), and cyclin D1 expression are regulated by the ERK pathway in lens cells after the extraction of fiber cells.
  • Ilieva Iliyana, Ohgami Kazuhiro, Jin Xue-Hai, Suzuki Yukari, Shiratori Kenji, Yoshida Kazuhiko, Kase Satoru, Ohno Shigeaki
    Experimental Eye Research 83 3 651 - 657 Elsevier B.V. 2006年09月 
    Captopril is an inhibitor of angiotensin-converting enzyme (ACE) that is largely used in the treatment of cardiovascular diseases. Several previous studies have demonstrated that captopril exhibits a wide variety of biological activities, including an anti-inflammatory action, on which we focused our attention. The aim of the present study was to investigate the efficacy of captopril on endotoxin induced uveitis (EIU) in rats. We investigated its effect upon cellular infiltration and protein leakage, as well as on the concentration of tumor necrosis factor-α (TNF-α), nitric oxide (NO), prostaglandin E2 (PGE2), monocyte chemoattractant protein-1 (MCP-1) in the anterior chamber. In addition, we checked its effect on activation of nuclear factor kappa B (NF-κB) in iris and ciliary body (ICB) cells in vivo. EIU was induced in male Lewis rats by a footpad injection of lipopolysaccharide (LPS). One hour after the LPS inoculation, either 1 mg/kg, 10 mg/kg or 100 mg/kg captopril were injected intravenously. 24 h later, the aqueous humor was collected from both eyes, and the number of infiltrating cells and protein concentration in the aqueous humor were determined. Levels of TNF-α, PGE2, NO and MCP-1 were determined by enzyme-linked immunosorbent assay. On some eyes, after enucleation, immunohistochemical staining with a monoclonal antibody against activated NF-κB was performed. Captopril treatment significantly decreased the inflammatory cells infiltration, the level of protein, concentrations of TNF-α, PGE2, NO and MCP-1 in the aqueous humor. The number of activated NF-κB-positive cells was lower in ICB of the rats treated with captopril 3 h after the LPS injection. The present results indicate that captopril suppresses the inflammation in EIU by inhibiting the NF-κB-dependent pathway and the subsequent production of pro-inflammatory mediators.
  • Nobuyoshi Kitaichi, Toshihide Ariga, Satoru Kase, Kauzhiko Yoshida, Kenichi Namba, Shigeaki Ohno
    Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 244 4 433 - 7 2006年04月 [査読有り][通常論文]
     
    BACKGROUND: KL-6 is a human glycoprotein secreted by type II alveolar cells in the lung, and its serum levels increase in pneumonia of various causes. We previously reported that serum KL-6 levels in uveitis patients with sarcoidosis were significantly higher than those of other uveitis patients and healthy controls. Additionally, the combined measurement of serum KL-6 and angiotensin converting enzyme (ACE) was useful for screening uveitic patients to diagnose sarcoidosis. The purpose of the present study was to investigate the clinical usefulness of quantifying serum KL-6 levels for following-up the patients with sarcoidosis. METHODS: Sera were obtained from 36 uveitic patients diagnosed with sarcoidosis and the same number of healthy volunteers. To examine the influence of systemic medication, we also collected blood samples from four more sarcoidosis patients, who were systemically treated with corticosteroid or angiotensin converting enzyme (ACE) inhibitor, an anti-hypertensive drug. The serum concentration of KL-6 was measured by a human KL-6 electrochemiluminescence immunoassay (ECLIA). RESULTS: The mean KL-6 concentrations of sarcoidosis patients and healthy controls were 449.3+/-66.3 (mean+/-SE) and 192.1+/-11.3, respectively. The average levels of serum KL-6 were significantly elevated in sarcoidosis patients compared with healthy control subjects (P<0.001), and there were significant correlations between serum KL-6 and ACE levels in the patients with sarcoidosis (r=0.70 and P<0.0001). Moreover, serum KL-6 concentrations were less affected by systemic corticosteroid, and unaffected by ACE inhibitory drugs in contrast to ACE levels. CONCLUSIONS: Measurement of serum KL-6 in the uveitic patients may be useful to follow-up the diagnosed sarcoidosis, as well as for diagnosing sarcoidosis, because the serum KL-6 level was well correlated with the ACE level, and less affected by systemic medication than ACE levels.
  • S Kase, K Yoshida, T Harada, C Harada, K Namekata, Y Suzuki, K Ohgami, K Shiratori, KI Nakayama, S Ohno
    GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY 244 3 352 - 358 2006年03月 [査読有り][通常論文]
     
    Purpose: The roles of the extracellular signal-regulated kinase (ERK) pathway in the expression of cyclin D1 and p27(KIP1), the phosphorylation of p27(KIP1), and proliferation activity were examined after retinal detachment. Methods: Normal eyes and eyes at 15 min, 2 and 4 days after retinal detachment in C57Bl6 mice were examined by immunohistochemistry using anti-phosphorylated (p) ERK1/2, anti-cyclin D1, anti-p27(KIP1), anti-p27(KIP1) phosphorylated at serine 10 (S10-phospho-p27), and anti-proliferating cell nuclear antigen (PCNA) antibodies with or without treatment with a specific ERK inhibitor, PD98059. Mouse Muller cells were isolated and examined for alteration of p27(KIP1) and cyclin D1 after exposure of basic fibroblast growth factor (bFGF) with and without treatment of PD98059 using Western blotting. Results: In the normal retina, nuclear immunoreactivity for p27(KIP1), but not S10-phospho-p27 or pERK1/2, was observed in the middle sublayer of the inner nuclear layer (INL), where Muller glial cells are situated. At 15 min after the retinal detachment, p27(KIP1), S10-phospho-p27 and pERK1/2-positive nuclei were noted in the INL, whereas immunoreactivity for pERK1/2 or S10-phospho-p27 was not observed after treatment with PD98095. Cyclin D1 was induced in the INL 2 days after the retinal detachment, and the induction was inhibited by PD98059. At 4 days after the detachment, p27(KIP1) immunoreactivity was not observed, and cyclin D1 and PCNA were expressed. The disappearance of p27(KIP1) was suppressed, whereas expression of cyclin D1 and PCNA was not observed in mice treated with PD98059. Exposure of bFGF relatively decreased the expression level of p27(KIP1) and increased the level of cyclin D1 in mouse Muller cells, compared with control level. Induction of cyclin D1 and decrease in p27(KIP1) were inhibited with treatment of PD98059. Conclusion: Phosphorylation of ERK and expression of p27(KIP1) and cyclin D1 are involved in the proliferation of Muller cells after retinal detachment.
  • Suzuki Yukari, Ohgami Kazuhiro, Shiratori Kenji, Jin Xue-Hai, Ilieva Iliyana, Koyama Yoshikazu, Yazawa Kazunaga, Yoshida Kazuhiko, Kase Satoru, Ohno Shigeaki
    Experimental Eye Research 82 2 275 - 281 Elsevier Ltd. 2006年02月 
    We investigated the effects of astxanthin (AST), a carotenoid, on endotoxin-induced uveitis (EIU), and measured the expression of inflammatory cytokines and chemokines in the presence or absence of AST over the course of the disease. EIU was induced in male Lewis rats by footpad injection of lipopolysaccharide (LPS). Immediately after the LPS inoculation, either 1, 10, or 100 mg/kg of AST were injected intravenously. Aqueous humor was collected at 6, 12 and 24 hours after LPS inoculation and the number of infiltrating cells in the anterior chamber were counted. In addition, we assayed the concentration of protein, nitric oxide (NO), tumor necrosis factor (TNF)- and prostaglandin (PG) E2. Immunohistochemical staining with a monoclonal antibody against activated NF-B was performed in order to evaluate the effects of AST on NF-B activation. Rats injected with AST showed a significant decrease in the number of infiltrating cells in anterior chamber. Moreover, AST-treated rats with EIU showed significantly lower concentrations of protein, NO, TNF- and PGE2 in the aqueous humor. Even the early stages of EIU were suppressed by injection of AST. The number of activated NF-B-positive cells was lower in iris-ciliary bodies treated with 10 or 100 mg/kg AST at 3 hours after LPS injection. These results suggest that AST reduces ocular inflammation in eyes with EIU by downregulating proinflammatory factors and by inhibiting the NF-B-dependent signaling pathway.
  • Kase S, Saito W, Yokoi M, Yoshida K, Furudate N, Muramatsu M, Saito A, Kase M, Ohno S
    British Journal of Ophthalmology 90 1 96 - 98 BMJ Publishing Group 2006年01月 
    Background/aim: The mechanisms of the cellular origin and cell proliferation in the idiopathic epiretinal membrane (ERM) are unsolved. The aim of this study was to examine the expression of cell cycle related molecules and glutamine synthetase (GS), which is expressed in Müller cells and their processes, in ERM tissues. Methods: The ERMs were surgically removed using pars plana vitrectomy. Formalin fixed, paraffin embedded ERM tissues were analysed by immunohistochemistry with anti-cyclin D1, p27 (KIP1), proliferating cell nuclear antigen (PCNA), and GS antibodies. Results: The histopathological findings showed that all the ERMs consisted of oval or spindle mononuclear cells with thin collagen-like tissues. Immunoreactivity for GS was detected in collagen-like tissues of ERM, presenting a continuous, isodense pattern. GS immunopositive cells in all cases expressed PCNA in their nuclei. Nuclear immunoreactivity for cyclin D1 was noted in the ERM constituent cells, whereas p27 (KIP1) positive nuclei were not detected. Conclusion: Cyclin D1 and PCNA were expressed in the idiopathic ERM, which was mainly derived from Müller cells and extensions of their processes.
  • Satoru Kase, Kazuhiko Yoshida, Masaharu Sakai, Kazuhiro Ohgami, Kenji Shiratori, Nobuyoshi Kitaichi, Yukari Suzuki, Takayuki Harada, Shigeaki Ohno
    Acta histochemica 107 6 469 - 72 2006年 [査読有り][通常論文]
     
    The maf gene encodes a transcription factor protein containing a typical basic/leucine zipper domain structure, a motif for protein dimerization and DNA binding. It has been demonstrated that maf family genes have important roles in embryonic development and cellular differentiation. In this study, localization of cyclin D1, one of the cell cycle-related molecules, was examined immunohistochemically in developing lens cells of c-maf knockout (-/-) mice. At embryonic day 14 in wild-type mice, lens cells consisted of round epithelial cells in a single layer and regularly arranged elongated lens cells, indicating primary lens fiber cells. Cyclin D1-positive nuclei were observed in the lens epithelial cells, whereas cyclin D1 was not detected in the primary lens fiber cells. In c-maf -/- mice, a variety of round epithelial cells were located in the anterior and posterior lens. Many cyclin D1-positive nuclei were observed in lens epithelial cells as well as posterior lens cells. These results are consistent with c-maf playing a role in the regulation of cyclin D1 in developing lens cells.
  • S Kase, K Yoshida, K Ohgami, K Shiratori, T Harada, S Ohno
    ANTICANCER RESEARCH 25 6B 3843 - 3846 2005年11月 [査読有り][通常論文]
     
    Background: Retinoblastoma is a rare cancer of the eye, in which biallelic inactivation of the retinoblastoma gene is a hallmark. Although retinoblastoma protein (Rb) and p27(KIP1) block the cell cycle transition from G1- to S-phase, the interaction has not been confirmed in vivo. The aim of this study was to examine the correlation between the expression of p27(K[PI) and cell proliferation in human retina and retinoblastoma. Materials and Methods: Human retinoblastoma, surgically removed, was fixed by 4% paraformaldehyde. Then, paraffin-embedded tissue sections were examined using immunohistochemistry with antip27(KIP1) and anti-proliferating cell nuclear antigen (PCNA) antibodies. Results: Retinoblastoma tissue was adjacent to the normal retina in which tumor cells with homogeneous nuclei proliferated and it was impossible to identify the layer structure of the inner nuclear layer (INL) and the outer nuclear layer (ONL). In normal retina, PCNA-positive nuclei were not observed, whereas nuclear immunoreactivity for PCNA was detected in a variety of tumor cells. Many p27(KIP1) -positive nuclei were detected in INL and ONL, while p27(KIP1) immunoreactivity was not detected in retinoblastoma cells. Conclusion: The correlation between disappearance of p27(KIP1) and induction of proliferation activity suggests that functional loss of Rb leads to down-regulation of p27(K[P1) and uncontrolled retinal cell proliferation.
  • W Saito, S Kase, K Yoshida, H Ohguro, M Yokoi, H Iwaki, S Ohno
    AMERICAN JOURNAL OF OPHTHALMOLOGY 140 5 942 - 945 2005年11月 [査読有り][通常論文]
     
    PURPOSE: To describe a patient with bilateral diffuse uveal melanocytic proliferation (BDUMP) and cancer-associated retinopathy (CAR). DESIGN: Interventional case report. METHODS: A 66-year-old woman developed progressive vision loss 4 months after total hysterectomy. Ophthalmologic examination, Western blot test of sera and aqueous humor, and immunohistochemistry of carcinoma cells were performed. RESULTS: Testing revealed BDUMP and severe retinal dysfunction. Autoantibodies against recoverin and heat shock cognate protein 70 (hsc 70) were detected in serum. Cytoplasmic immunoreactivity for recoverin and hsc 70 was observed in endometrioid carcinoma cells. CONCLUSIONS: Simultaneous cases of BDUMP and CAR are rare. Aberrantly expressed recoverin and hsc 70 triggered serum autoantibody production, which caused photoreceptor degeneration.
  • Satoru Kase, Wataru Saito, Kazuhiko Yoshida, Kenichi Namba, Mitsuhiko Osaki, Kazuhiro Ohgami, Kenji Shiratori, Nobuyoshi Kitaichi, Hironobu Adachi, Hisao Ito, Shigeaki Ohno
    Pathology international 55 9 569 - 73 2005年09月 [査読有り][通常論文]
     
    Reported herein is a case of 62-year-old man who complained of blurred vision and ocular pain in his right eye. The patient was diagnosed with choroidal melanoma complicated by neovascular glaucoma (NVG) and total retinal detachment, and he underwent enucleation of the eye. The isolated tumor was 2.5 x 2.5 cm in size. It was accompanied by intratumoral calcification, and consisted of epithelioid and spindle melanoma cells. There were a variety of microvessels in the stroma of the iris. The expression of thymidine phosphorylase (dThdPase), an angiogenic factor, was examined immunohistochemically. Cytoplasmic immunoreactivity for dThdPase was more prominent in the epithelioid cells than in spindle tumor cells. Another case of choroidal melanoma without NVG had less marked immunoreactivity. These results suggest that the production of dThdPase by melanoma cells correlates with the pathogenesis of NVG.
  • Kase Satoru, Yoshida Kazuhiko, Nakayama Keiichi I, Nakayama Keiko, Ikeda Hiromi, Harada Takayuki, Harada Chikako, Ohgami Kazuhiro, Shiratori Kenji, Ohno Shigeaki
    Int J Mol Med 16 2 257 - 262 2005年08月 [査読有り][通常論文]
  • Kase Satoru, Yoshida Kazuhiko, Ikeda Hiromi, Harada Takayuki, Harada Chikako, Imaki Junko, Ohgami Kazuhiro, Shiratori Kenji, Nakayama Keiichi I, Nakayama Keiko, Ohno Shigeaki
    Curr Eye Res 30 6 437 - 442 2005年06月 [査読有り][通常論文]
  • Kase S, Namba K, Kitaichi N, Ohno S
    British Journal of Ophthalmology 90 2 244 - 245 BMJ Publishing Group Ltd 2005年 
    Nasal natural killer (NK)/T cell lymphoma is a definitive diagnostic entity in the World Health Organization lymphoma classification.1 In many cases, NK/T cell lymphoma is invariably associated with Epstein-Barr virus (EBV). Although ocular involvement is found in less than 10% of patients with systemic lymphoma,2 because of its anatomical proximity, nasal NK/T lymphoma can sometimes complicate uveitis and orbital infiltration.3 We experienced a case of nasal NK/T lymphoma, and the cells collected from the aqueous humour originated from the lymphoma which was infected by EBV.
  • Kazuhiro Ohgami, Iliyana Ilieva, Kenji Shiratori, Yoshikazu Koyama, Xue-Hai Jin, Kazuhiko Yoshida, Satoru Kase, Nobuyoshi Kitaichi, Yukari Suzuki, Tsuneo Tanaka, Shigeaki Ohno
    Investigative ophthalmology & visual science 46 1 275 - 81 2005年01月 [査読有り][通常論文]
     
    PURPOSE: Aronia crude extract (ACE) with high levels of polyphenol compounds has been reported to have antioxidative effects in vitro and in vivo. In this study, attention was focused on the antioxidant effect of ACE. The purpose of the present study was to investigate the effect of ACE on endotoxin-induced uveitis (EIU) in rats. In addition, the endotoxin-induced expression of the inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 proteins was investigated in a mouse macrophage cell line (RAW 264.7) treated with ACE in vitro, to clarify the anti-inflammatory effect. METHODS: EIU was induced in male Lewis rats by a footpad injection of lipopolysaccharide (LPS). Immediately after the LPS inoculation, 1, 10, or 100 mg ACE or 10 mg prednisolone was injected intravenously. After 24 hours, the aqueous humor was collected from both eyes, and the number of infiltrating cells, protein concentration, nitric oxide (NO), prostaglandin (PG)-E2, and TNF-alpha levels in the aqueous humor were determined. RAW 264.7 cells treated with various concentrations of ACE were incubated with 10 mug/mL LPS for 24 hours. Levels of NO, PGE2, and TNF-alpha were determined by an enzyme-linked immunosorbent assay. The expression of iNOS and COX-2 proteins was analyzed by Western blot analysis. RESULTS: The number of inflammatory cells, the protein concentrations, and the levels of NO, PGE2, and TNF-alpha in the aqueous humor in the groups treated with ACE were significantly decreased in a dose-dependent manner. In addition, the anti-inflammatory effect of 100 mg ACE was as strong as that of 10 mg prednisolone. The anti-inflammatory action of ACE was stronger than that of either quercetin or anthocyanin administered alone. ACE also suppressed LPS-induced iNOS and COX-2 protein expressions in RAW 264.7 cells in vitro in a dose-dependent manner. CONCLUSIONS: The results suggest that ACE has a dose-dependent anti-ocular inflammatory effect that is due to the direct blocking of the expression of the iNOS and COX-2 enzymes and leads to the suppression of the production of NO, PGE2, and TNF-alpha.
  • S Kase, J Imaki, T Harada, C Harada, K Ohgami, K Shiratori, M Sakai, S Nishi, S Ohno, K Yoshida
    ANATOMY AND EMBRYOLOGY 209 2 153 - 156 2004年12月 [査読有り][通常論文]
     
    Maf encodes a transcription factor protein containing a typical basic leucine zipper domain structure, a motif for protein dimerization and DNA binding. We examined the expression of maf-B mRNA in the epithelium around the eyelid closure. Expression of maf-B mRNA was examined in C57Bl6 mice at the embryonic stages in 12.5 days of gestation (E12.5) and E18 using in situ hybridization with S-35-labeled antisense riboprobes. In embryos studied 12.5 days postconception, a message specific for maf-B was not detected around the developing eyelid. In contrast, maf-B was strongly expressed in the epithelium of the eyelid closure at E18. Expression of maf-B was strongly noted in the suprabasal differentiating cells derived from the basal layer of the conjunctiva and epidermis. In contrast, basal cells in the eyelid closure and in the epidermis, as well as keratinizing cells, did not express maf-B. These data indicate that maf-B mRNA is expressed during development of the eyelid closure.
  • S Kase, K Aoki, T Harada, C Harada, K Ohgami, K Shiratori, S Nishi, S Ohno, K Yoshida
    BRITISH JOURNAL OF OPHTHALMOLOGY 88 7 947 - 949 2004年07月 [査読有り][通常論文]
     
    Aim: To examine the expression of p65, one of nuclear factor-kappa B (NF-kappaB), in the conjunctival epithelium of the C57Bl6 mouse and a patient with epidemic keratoconjunctivitis (EKC). Methods: Normal and epithelial scraped cornea obtained 6 hours after the injury were processed for paraffin section. Samples of a normal and an EKC conjunctival epithelium were obtained using impression cytology. Both samples were analysed by immunocytochemistry using anti-p65 antibody. Results: Immunocytochemistry with the anti-NF-kappaB p65 antibody revealed that p65 was localised in the cytoplasm of the conjunctival epithelium in the C57Bl6 mouse without the treatment. Six hours after the scraping of the cornea, p65 protein was expressed in the nuclei of the conjunctival epithelium. p65 was localised in the cytoplasm of the conjunctival epithelium in the human normal eye. p65 protein was expressed in the nuclei of the conjunctival epithelial cells in the EKC patient. Conclusion: These findings suggest that NF-kappaB was activated in the conjunctiva in the epithelial scraping of the mouse cornea and in human EKC.
  • Yoshida Kazuhiko, Kase Satoru, Nakayama Keiko, Nagahama Hiroyasu, Harada Takayuki, Ikeda Hiromi, Harada Chikako, Imaki Junko, Ohgami Kazuhiro, Shiratori Kenji, Ilieva Iliyana Bozhidarova, Ohno Shigeaki, Nishi Shinzo, Nakayama Keiichi I
    Invest Ophthalmol Vis Sci 45 7 2163 - 2167 2004年07月 [査読有り][通常論文]
  • Yoshida Kazuhiko, Kase Satoru, Nakayama Keiko, Nagahama Hiroyasu, Harada Takayuki, Ikeda Hiromi, Harada Chikako, Imaki Junko, Ohgami Kazuhiro, Shiratori Kenji, Ohno Shigeaki, Nakayama Keiichi I
    Graefes Arch Clin Exp Ophthalmol 242 5 437 - 441 2004年05月 [査読有り][通常論文]
  • Yoshida Kazuhiko, Nakayama Keiko, Kase Satoru, Nagahama Hiroyasu, Harada Takayuki, Ikeda Hiromi, Harada Chikako, Imaki Junko, Ohgami Kazuhiro, Shiratori Kenji, Ohno Shigeaki, Nishi Shinzo, Nakayama Keiichi I
    Anat Embryol (Berl) 208 2 145 - 150 2004年05月 [査読有り][通常論文]

その他活動・業績

  • 福津佳苗, 齋藤理幸, 野田航介, 村田美幸, 加瀬諭, 柴涼介, 磯貝直己, 道家充, 石田晋 日本眼循環学会講演抄録集 36th 2019年
  • 野田 航介, 村田 美幸, 稲福 沙織, 松田 剛, 吉田 志帆, 董 陽子, 木下 哲志, 安藤 亮, 藤谷 顕雄, 齋藤 理幸, 董 震宇, 森 祥平, 加瀬 諭, 吉澤 史子, 齋藤 航, 神田 敦宏, 石田 晋, 眞島 行彦, 笹瀬 智彦, 天野 麻穂, 大橋 哲, 西村 伸一郎, 今川 貴仁, 白仁田 明生 日本眼科学会雑誌 122 (3) 223 -248 2018年03月 [査読無し][通常論文]
     
    近年の基礎研究は、血管内皮増殖因子(vascular endothelial growth factor:VEGF)が糖尿病網膜症の病態形成に主要な役割を演じることを明らかとした。そして、同分子群に対する阻害薬の臨床応用は糖尿病網膜症の治療予後を劇的に改善し、現在我々はanti-VEGF eraと呼ばれるこの時代において同疾患の治療体系が刻々と変貌するのを目の当たりにしている。かつては光凝固と硝子体手術のみが進行した糖尿病網膜症に対する治療手段であったことを考えると隔世の感がある。しかしながらその一方で、情報システムの革新と研究技術の進歩を背景に蓄積される基礎および臨床研究の成果は、網膜症病態の複雑さ、VEGF単独阻害による治療の限界、そしてその弊害の可能性なども浮き彫りにした。そして、その必然としてVEGF以外の病態責任分子を標的とした糖尿病網膜症に対する創薬研究が全世界で現在行われ、複数の分子標的製剤が糖尿病網膜症の治療オプションとなるpost anti-VEGF eraが目前に迫ってきている。糖尿病網膜症の発症および進展には、慢性炎症、そして酸化ストレスの関与が知られている。本研究においては、糖鎖など新規標的分子の探索的研究を行うとともに、この二つの病態に関わる分子としてvascular adhesion protein-1(VAP-1)/semicarbazide sensitive amine oxidase(SSAO)の糖尿病網膜症病態における役割についての検討を主に行った。VAP-1/SSAOは血管内皮細胞に発現する白血球接着分子だが、その一方で酵素活性も持つ多機能蛋白質"moonlighting protein"であり、慢性炎症と酸化ストレスの双方に関わる重要な分子の一つである。本研究ではVAP-1/SSAOが糖尿病網膜症の病態形成に白血球接着分子として関与する一方、遊離型蛋白質としてその眼内に蓄積すること、そしてその機序にVEGFや蛋白質分解酵素matrix metalloproteinasesが関与することを明らかにした。また、VAP-1/SSAOは酵素として過酸化水素および不飽和アルデヒドの一種アクロレインを産生し、血管内皮細胞における酸化ストレス亢進に寄与することとその機序を見出した。以上の検討結果に基づいて、本稿では糖尿病網膜症におけるVAP-1/SSAO阻害剤による治療可能性について述べたい。(著者抄録)
  • 視神経乳頭黒色細胞腫のOCT angiography所見
    菊地 郁, 加瀬 諭, 石田 晋 日本眼科学会雑誌 122 (臨増) 279 -279 2018年03月 [査読無し][通常論文]
  • 増殖糖尿病網膜症患者の硝子体中アクロレイン結合蛋白FDP-lysine濃度
    森 祥平, 村田 美幸, 野田 航介, 鈴木 智浩, 齋藤 理幸, 安藤 亮, 加瀬 諭, 齋藤 航, 神田 敦宏, 石田 晋 眼科臨床紀要 10 (11) 920 -921 2017年11月 [査読無し][通常論文]
  • PDTトリプル療法を行った加齢黄斑変性における治療2年後視力の規定因子
    安藤 亮, 野田 航介, 廣岡 季里子, 橋本 勇希, 鈴木 智浩, 森 祥平, 齋藤 理幸, 吉澤 史子, 加瀬 諭, 齋藤 航, 石田 晋 眼科臨床紀要 10 (11) 940 -940 2017年11月 [査読無し][通常論文]
  • ステロイドパルス療法が著効した脈絡膜新生血管とAZOORを伴った点状脈絡膜内層症の1例
    鈴木 智浩, 加瀬 諭, 森 祥平, 安藤 亮, 齋藤 理幸, 野田 航介, 石田 晋 眼科臨床紀要 10 (11) 949 -950 2017年11月 [査読無し][通常論文]
  • 難治性黄斑円孔に対する内境界膜自家移植変法
    柴田 有紀子, 齋藤 理幸, 藤谷 顕雄, 鈴木 智浩, 安藤 亮, 森 祥平, 加瀬 諭, 野田 航介, 石田 晋 眼科臨床紀要 10 (10) 843 -843 2017年10月 [査読無し][通常論文]
  • Pachychoroid pigment epitheliopathyの臨床像
    廣岡 季里子, 齋藤 航, 齋藤 理幸, 森 祥平, 安藤 亮, 橋本 勇希, 加瀬 諭, 野田 航介, 石田 晋 眼科臨床紀要 10 (10) 860 -860 2017年10月 [査読無し][通常論文]
  • 糖尿病眼における熱ショック蛋白α-クリスタリンと最終糖化産物の発現
    加瀬 諭, 石田 晋 糖尿病合併症 31 (Suppl.1) 341 -341 2017年10月 [査読無し][通常論文]
  • 瞼板内角質嚢胞との鑑別を要した眼瞼結膜嚢胞性病変の1例
    水門 由佳, 加瀬 諭, 石嶋 漢, 高桑 恵美, 石田 晋 日本眼腫瘍学会誌 6 1 -4 2017年09月 [査読無し][通常論文]
     
    【緒言】瞼板内角質嚢胞は、瞼板内に発生する腫瘤性病変において代表的な嚢胞性疾患である。今回我々は、瞼板内角質嚢胞と鑑別を要し、眼瞼結膜に発生した嚢胞性病変の1例を経験したので報告する。【症例】62歳女性。6年前から右上眼瞼の腫脹と自然排膿があり、前医にて経過観察を行ってきた。腫瘤が増大傾向を示したため、眼瞼脂腺癌などの悪性疾患が疑われ、当科紹介となった。初診時、右眼の上眼瞼結膜側に突出する黄色腫瘤がみられた。同日、眼瞼結膜から腫瘤の切除生検を行った。腫瘤の本体は瞼板内にみられ、病理組織検査では、一部に顆粒層を有する異型に乏しい重層扁平上皮が嚢胞状構造を形成しており、眼瞼結膜に隣接していた。嚢胞内腔には層板状の角化物が見られ、病理組織学的には表皮嚢胞を考える所見であった。【結論】上眼瞼の代表的な嚢胞性疾患として、表皮嚢胞、瞼板内角質嚢胞が挙げられる。本症例は、臨床的に開口部が結膜と考えられること、嚢胞壁に顆粒層を有することから表皮嚢胞、瞼板内角質嚢胞とは異なる結膜嚢胞性病変である。(著者抄録)
  • 非典型的所見を呈した片眼性網膜芽細胞腫の1例
    安藤 亮, 加瀬 諭, 野崎 真世, 石田 晋 眼科臨床紀要 10 (6) 517 -517 2017年06月 [査読無し][通常論文]
  • 堤 雅幸, 堀江 幸弘, 加瀬 諭, 北市 伸義 臨床眼科 71 (5) 789 -794 2017年05月
  • 眼付属器MALTリンパ腫の診断におけるフローサイトメトリの有用性
    加瀬 諭, 石嶋 漢, 浦木 健彦, 鈴木 康夫, 石田 晋 日本眼科学会雑誌 121 (臨増) 201 -201 2017年03月 [査読無し][通常論文]
  • 多発消失性白点症候群における脈絡膜層別厚の経時変化
    橋本 勇希, 齋藤 航, 長谷川 裕香, 齋藤 理幸, 安藤 亮, 森 祥平, 加瀬 諭, 野田 航介, 石田 晋 日本眼科学会雑誌 121 (臨増) 218 -218 2017年03月 [査読無し][通常論文]
  • 腫瘍性病変が疑われた結節性後部強膜炎の1例
    柴田 有紀子, 加瀬 諭, 南場 研一, 石田 晋 日本眼科学会雑誌 121 (臨増) 329 -329 2017年03月 [査読無し][通常論文]
  • 睫毛乱生に対するラジオ波メス睫毛根焼灼の治療効果
    浦木 健彦, 加瀬 諭, 木下 哲志, 石嶋 漢, 石田 晋 眼科手術 30 (1) 187 -190 2017年01月 [査読無し][通常論文]
     
    目的:睫毛乱生に対するラジオ波メスを用いた睫毛根焼灼の治療成績を報告する。方法:2015年3〜12月に帯広協会病院にてラジオ波メスを用いた睫毛根焼灼を施行し睫毛乱生13例21側を対象とした。機器はサージトロンEMC(Ellman社)を使用し、焼灼条件は止血・凝固モード、パワーは2W、焼灼時間は1秒とした。焼灼後56日間で再発がみられない場合に寛解と定義した。結果:初回治療では151本中111本が寛解した(寛解率:73.5%)。再発した40本に対し2回目の治療を施行し、32本が寛解した(寛解率:80%)。再度、再発した8本に3回目の治療を施行し、結果的に100%の寛解率を得た。治療回数が多い眼瞼では、有意に睫毛数が増加していた。合併症では21側中2側(9.5%)に軽微な色素沈着や陥凹瘢痕がみられた。結論:本研究により、睫毛乱生に対するラジオ波焼灼は、有用な治療法の一つであることが示された。(著者抄録)
  • PDTトリプル療法を行ったポリープ状脈絡膜血管症における治療1年後視力の規定因子
    安藤 亮, 齋藤 航, 廣岡 季里子, 鈴木 智浩, 吉澤 史子, 齋藤 理幸, 加瀬 諭, 森 祥平, 野田 航介, 石田 晋 眼科臨床紀要 9 (11) 930 -930 2016年11月 [査読無し][通常論文]
  • アフリベルセプト併用PDTトリプル療法1年後の治療成績
    鈴木 智浩, 齋藤 航, 森 祥平, 齋藤 理幸, 安藤 亮, 加瀬 諭, 廣岡 季里子, 吉澤 史子, 野田 航介, 石田 晋 眼科臨床紀要 9 (11) 931 -931 2016年11月 [査読無し][通常論文]
  • ベバシズマブ硝子体内注射が奏効した血管増殖性網膜腫瘍の3例
    川向 友子, 齋藤 航, 加瀬 諭, 石田 晋 眼科臨床紀要 9 (11) 934 -934 2016年11月 [査読無し][通常論文]
  • Michiyuki Saito, Kousuke Noda, Yuki Hashimoto, Kiriko Hirooka, Zhenyu Don, Ryo Ando, Shohei Mori, Satoru Kase, Wataru Saito, Susumu Ishida INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 57 (12) 2016年09月 [査読無し][通常論文]
  • 糖尿病網膜症の増殖組織における分子シャペロンαB-クリスタリンのリン酸化
    加瀬 諭, 董 陽子, 神田 敦宏, 野田 航介, 石田 晋 糖尿病合併症 30 (Suppl.1) 249 -249 2016年09月 [査読無し][通常論文]
  • 中心性漿液性脈絡網膜症における中心窩脈絡膜厚と黄斑部脈絡膜血流の変化
    齋藤 理幸, 野田 航介, 橋本 勇希, 廣岡 季里子, 安藤 亮, 森 祥平, 加瀬 諭, 齋藤 航, 石田 晋 日本眼科学会雑誌 120 (臨増) 188 -188 2016年03月 [査読無し][通常論文]
  • 慢性中心性漿液性脈絡網膜症における脈絡膜循環と形態の経時変化
    廣岡 季里子, 齋藤 航, 齋藤 理幸, 橋本 勇希, 森 祥平, 加瀬 諭, 安藤 亮, 野田 航介, 石田 晋 日本眼科学会雑誌 120 (臨増) 242 -242 2016年03月 [査読無し][通常論文]
  • 横山 英恵, 加瀬 諭, 鈴木 康夫, 勝田 聡, 高橋 光生, 篠原 敏也, 石田 晋, 加瀬 学 臨床眼科 69 (10) 1545 -1550 2015年10月 [査読無し][通常論文]
     
    背景:硝子体浸潤を伴う脈絡膜悪性黒色腫はわが国では稀である。目的:硝子体浸潤を伴う脈絡膜悪性黒色腫の1例の報告。症例:73歳の男性が左眼の眼底の隆起性病変で紹介受診した。2年前から左眼の飛蚊症を自覚していた。所見と経過:矯正視力は左右眼とも0.6であった。左眼には前部硝子体に色素細胞が浮遊し,眼底耳側に3乳頭径大の茶褐色隆起性病変があり,その頂点に黒褐色病巣があった。この隆起性病変は,フルオレセイン蛍光眼底造影の後期で色素漏出,インドシアニングリーン蛍光造影で過蛍光であり,黒褐色病巣は終始低蛍光であった。悪性黒色腫と診断し,左眼を摘出した。病理学的に,類上皮型の脈絡膜悪性黒色腫であり,腫瘍の大きさは8mm×8mm×5mmで,腫瘤の頂点で腫瘍細胞が網膜を穿破して硝子体腔に浸潤していた。結論:本症例はわが国では稀な,硝子体浸潤を伴う脈絡膜悪性黒色腫であった。(著者抄録)
  • 加瀬 諭, 石田 晋 あたらしい眼科 32 (8) 1075 -1081 2015年08月 [査読無し][通常論文]
  • 結膜節外辺縁帯B細胞性リンパ腫におけるレニン・アンジオテンシン系の病態への関与
    石塚 タンエルダル, 神田 敦宏, 加瀬 諭, 安藤 亮, 董 陽子, 稲福 沙織, 田川 義晃, 野田 航介, 石田 晋 日本眼科学会雑誌 119 (臨増) 180 -180 2015年03月 [査読無し][通常論文]
  • Satoru Kase, Toshiya Shinohara, Manabu Kase JAMA OPHTHALMOLOGY 132 (8) 1021 -1022 2014年08月 [査読無し][通常論文]
  • 診断に苦慮した毛様体平滑筋腫の一例
    石嶋 漢, 加瀬 諭, 吉川 洋, 鈴木 茂伸, 新明 康弘, 南場 研一, 山本 哲平, 野崎 真世, 野田 実香, 石田 晋 日本眼科学会雑誌 118 (臨増) 304 -304 2014年03月 [査読無し][通常論文]
  • 癌関連網膜症の臨床像
    齋藤 理幸, 齋藤 航, 加瀬 諭, 野田 航介, 吉沢 史子, 藤谷 顕雄, 大黒 浩, 石田 晋 眼科臨床紀要 6 (10) 808 -809 2013年10月 [査読無し][通常論文]
  • 中心窩に多発性裂孔を呈した黄斑円孔の1例
    鈴木 智浩, 野田 航介, 齋藤 航, 齋藤 理幸, 加瀬 諭, 藤谷 顕雄, 吉澤 史子, 石田 晋 眼科臨床紀要 6 (10) 830 -830 2013年10月 [査読無し][通常論文]
  • ラニビズマブ併用PDTトリプル療法1年後の治療成績
    吉澤 史子, 齋藤 航, 加瀬 諭, 齋藤 理幸, 藤谷 顕雄, 橋本 勇希, 野田 航介, 石田 晋 眼科臨床紀要 6 (10) 837 -838 2013年10月 [査読無し][通常論文]
  • 辻 英貴, 鈴木 茂伸, 加瀬 諭 眼科 55 (8) 865 -904 2013年08月
  • 黄斑円孔網膜剥離に対する硝子体手術成績 黄斑バックル使用の効果
    藤谷 顕雄, 齋藤 航, 齋藤 理幸, 吉沢 史子, 野田 航介, 加瀬 諭, 石田 晋 眼科手術 26 (2) 279 -283 2013年04月 [査読無し][通常論文]
     
    目的:黄斑円孔網膜剥離(MHRD)に対する硝子体手術(PPV)成績を検討すること。対象および方法:2003年12月から2011年8月に北海道大学病院眼科でPPVを施行したMHRD20例20眼(男性3例、女性17例、平均年齢69.5歳)を対象とした。初回術式として15眼に内境界膜(ILM)剥離併用PPV(PPV群)、5眼に黄斑バックル(MB)併用PPV(MB群)が施行された。網膜復位率、視力の推移、黄斑円孔閉鎖率などについて、診療録より後ろ向きに検討した。結果:PPV群の初回網膜復位率は66.7%であり、MHが再開通した3眼にMB併用PPVを追加し、全例で網膜復位を得た。一方、MB群の初回網膜復位率は80%、最終網膜復位術は100%であった。最終的に19眼(95%)で網膜は復位した。最終平均視力は有意に改善し(p=0.0007)、最終的にMB併用群は、非併用群より良好な傾向があった(p=0.069)。黄斑円孔閉鎖率は、MB併用群、非併用群でそれぞれ71.4%、40.0%であった。結論:MHRDに対するPPVにおける、長眼軸長眼でもMBを併用することで良好な網膜腹位率と良好な黄斑円孔閉鎖率が得られた。(著者抄録)
  • 網膜血管増殖性腫瘍に対する硝子体手術成績と血管内皮増殖因子の発現
    齋藤 航, 藤谷 顕雄, 加瀬 諭, 董 震宇, 石田 晋 眼科臨床紀要 5 (10) 942 -942 2012年10月 [査読無し][通常論文]
  • DNAメチル化阻害剤による脈絡膜血管内皮細胞の増殖抑制効果
    加瀬 諭, 園田 祥三, ヘー・シクン, ステファン・ライアン, ヒントン・デービット, 石田 晋 眼科臨床紀要 5 (10) 954 -954 2012年10月 [査読無し][通常論文]
  • 強度近視眼に発症したタモキシフェン網膜症の1例
    吉澤 史子, 加瀬 諭, 齋藤 航, 石田 晋 眼科臨床紀要 5 (10) 971 -971 2012年10月 [査読無し][通常論文]
  • 橋本 勇希, 野田 航介, 齋藤 航, 藤谷 顕雄, 齋藤 理幸, 加瀬 諭, 吉澤 史子, 石田 晋 眼科臨床紀要 5 (7) 651 -655 2012年07月 [査読無し][通常論文]
     
    背景:小児Coats病に対してbevacizumab硝子体内注射(以下;IVB)併用網膜光凝固を施行した一例の臨床経過報告。症例:12歳、男児。初診時矯正視力は右0.04で、眼底には右耳側周辺部に網膜毛細血管拡張と瘤状の異常網膜血管があった。異常血管周囲には強度の網膜浮腫があり、後極部および中心窩に硬性白斑が集積していた。フルオレセイン蛍光眼底造影(FA)では異常血管に一致した強い蛍光漏出を示した。Coats病stage 2Bと診断し、全身麻酔下でIVB(1.25mg)および網膜光凝固を施行した。治療4日後には黄斑浮腫と硬性白斑は軽減し、視力は0.3に改善した。その後、異常網膜血管に対する網膜光凝固を追加したところ、硬性白斑と網膜浮腫は著明に減少し、視力は1.0に改善した。結論:IVBを併用した網膜光凝固は、小児のCoats病において有効な治療法であることが示唆された。(著者抄録)
  • 加瀬 諭 あたらしい眼科 = Journal of the eye 29 (5) 649 -650 2012年05月30日 [査読無し][通常論文]
  • 加瀬 諭 あたらしい眼科 = Journal of the eye 29 (3) 361 -363 2012年03月30日 [査読無し][通常論文]
  • ヒト結膜MALTリンパ腫におけるVEGFの発現
    木下 哲志, 加瀬 諭, 安藤 亮, 董 震宇, 福原 淳一, アントン・レニコフ, 神田 敦宏, 野田 航介, 石田 晋 日本眼科学会雑誌 116 (臨増) 278 -278 2012年03月 [査読無し][通常論文]
  • 漿液性網膜色素上皮剥離がある滲出型加齢黄斑変性の臨床経過
    吉澤 史子, 齋藤 航, 藤谷 顕雄, 齋藤 理幸, 加瀬 諭, 野田 航介, 石田 晋 日本眼科学会雑誌 116 (臨増) 334 -334 2012年03月 [査読無し][通常論文]
  • 自己免疫性網膜症疑い患者におけるWestern blot法を用いた抗網膜抗体陽性率
    齋藤 理幸, 齋藤 航, 加瀬 諭, 野田 航介, 吉沢 史子, 藤谷 顕雄, 大黒 浩, 石田 晋 日本眼科学会雑誌 116 (臨増) 337 -337 2012年03月 [査読無し][通常論文]
  • 宇野 友絵, 南場 研一, 加瀬 諭, 齋藤 航, 北市 伸義, 大野 重昭, 石田 晋 あたらしい眼科 = Journal of the eye 29 (1) 135 -138 2012年01月30日 [査読無し][通常論文]
  • 山本 和幸, 加瀬 諭, 野田 実香, 岩口 佳史, 後藤田 裕子, 石田 晋 臨床眼科 66 (1) 57 -60 2012年01月 [査読無し][通常論文]
     
    目的:涙腺嚢胞の1症例の報告。症例:80歳男性が右の上眼瞼腫脹で受診した。40年前に涙嚢炎で右の涙嚢摘出を受けていた。所見:右の上眼瞼の耳側に直径10mmの表面が平滑な軟性腫瘤が触知された。周囲組織との癒着はなかった。磁気共鳴画像検査(MRI)のT2強調画像で,内部が均一な高信号を示す嚢胞様病変があった。血液検査でCRPとIgGの上昇があった。摘出した腫瘤は,病理組織学的に大小の嚢胞腔腫瘤からなり,嚢胞内腔は多列線毛円柱上皮を示し,断頭分泌を伴っていた。嚢胞の上皮下にリンパ球とIgG陽性の形質細胞浸潤があった。結論:本症例は涙嚢様組織を呈する涙腺嚢胞と考えられる。血液のCRPとIgG値の上昇,嚢胞の上皮下に浸潤した形質細胞がIgG陽性であったことから,その発生に慢性炎症が関与した可能性がある。(著者抄録)
  • 加瀬 諭 日本眼科學会雜誌 115 (11) 998 -1006 2011年11月10日 [査読無し][通常論文]
  • 加瀬 諭, 石嶋 漢, 野田 実香, 石田 晋 日本眼科學会雜誌 115 (11) 1043 -1047 2011年11月10日 [査読無し][通常論文]
  • 狭心症を合併した乳頭血管炎患者における冠動脈の病理学的検討
    加瀬 諭, 齋藤 航, 吉沢 史子, 矢野 俊之, 石田 晋 眼科臨床紀要 4 (10) 1002 -1002 2011年10月 [査読無し][通常論文]
  • 野崎 真世, 加瀬 諭, 吉田 和彦, 石嶋 漢, 野田 実香, 鈴木 茂伸, 東 範行, 石田 晋 臨床眼科 65 (7) 1123 -1127 2011年07月 [査読無し][通常論文]
     
    目的:網膜芽細胞腫の診断と臨床経過の報告。症例:過去8年間の網膜芽細胞腫の自験例7症例を検索した。結果:男児2例,女児5例で,5例が片眼性,2例が両眼性であった。年齢は6例が4歳以下で,1例が7歳であった。主訴は白色瞳孔と斜視が5例,視力低下が1例,結膜充血と眼瞼腫脹が1例にあった。国際分類での病期はB〜Eの範囲にあり,3例がE期であった。初回治療として眼球摘出術を5眼,眼窩内容除去術を1眼に行った。眼球を温存した3眼中,2眼では後に眼球摘出を必要とし,1眼では再発がなかった。眼球摘出術または眼窩内容除去術を行った6眼では転移はなかった。眼球外に浸潤した2例は不帰の転帰をとった。この2例は,初診時に網膜芽細胞腫の典型的所見がなかった。結論:網膜芽細胞腫の初診時の臨床像は,必ずしも予後を示さない。(著者抄録)
  • 横山 千秋, 森 祥平, 鎌田 麻子, 加瀬 諭, 石田 晋 臨床眼科 65 (6) 945 -948 2011年06月 [査読無し][通常論文]
     
    目的:急性涙腺炎を初発症状とした眼部帯状疱疹の1例の報告。症例:82歳女性が2日前からの右眼周囲の痛みで受診した。圧痛を伴う右眼瞼の発赤と腫脹があり,皮疹はなかった。磁気共鳴画像検査(MRI)の所見から急性涙腺炎を疑い,抗生物質を点滴した。4日後に涙腺腫脹が増悪し,その2日後に右角膜上皮に点状混濁と前房炎症が生じ,抗ウイルス薬治療を開始した。さらに2日後に右前額部に痂皮を伴う皮疹とびらんが生じ,帯状疱疹と診断した。初診から15日後に涙腺炎,前房の炎症,皮疹は寛解した。結論:典型的な皮疹や眼病変がなく,抗生物質に反応しない急性涙腺炎では,稀ではあるが眼部帯状疱疹による可能性がある。(著者抄録)
  • ヒト翼状片におけるTissue Factorの発現
    安藤 亮, 加瀬 諭, 大橋 勉, 董 震宇, 福原 淳一, アントン・レニコフ, 神田 敦宏, 村田 美幸, 野田 航介, 石田 晋 日本眼科学会雑誌 115 (臨増) 203 -203 2011年04月 [査読無し][通常論文]
  • AlphaB-crystallinによる実験的脈絡膜新生血管の制御
    加瀬 諭, 園田 祥三, 北村 瑞, Stephen Ryan, David Hinton, 石田 晋 日本眼科学会雑誌 115 (臨増) 219 -219 2011年04月 [査読無し][通常論文]
  • 増殖糖尿病網膜症の線維血管膜におけるalphaB-crystallinの発現
    董 震宇, 加瀬 諭, 安藤 亮, 福原 淳一, アントン・レニコフ, 神田 敦宏, 村田 美幸, 野田 航介, 斎藤 航, 石田 晋 日本眼科学会雑誌 115 (臨増) 231 -231 2011年04月 [査読無し][通常論文]
  • 石嶋 漢, 加瀬 諭, 野田 実香, 石田 晋 日本眼科學会雜誌 114 (12) 1036 -1039 2010年12月10日 [査読無し][通常論文]
  • 特発性網膜上膜におけるCyclooxygenase(COX)-2の発現
    加瀬 諭, 齋藤 航, 石田 晋 眼科臨床紀要 3 (10) 996 -996 2010年10月 [査読無し][通常論文]
  • 熱ショックタンパク質70発現量増加によるマウス紫外線角膜炎の回復(Amelioration of UV-photokeratitis in mice by heat shock protein 70 upregulation)
    アントン・レニコフ, 北市 伸義, 加瀬 諭, 石田 晋, 大野 重昭 日本眼科学会雑誌 114 (臨増) 246 -246 2010年03月 [査読無し][通常論文]
  • くも膜下腔に浸潤したびまん性浸潤型網膜芽細胞腫の一例
    吉田 和彦, 加瀬 諭, 野崎 真世, 石田 晋 日本眼科学会雑誌 114 (臨増) 258 -258 2010年03月 [査読無し][通常論文]
  • 眼瞼脂腺癌におけるalpha-crystallinの発現
    加瀬 諭, 吉田 和彦, 野田 実香, Rao Narsing, 石田 晋 日本眼科学会雑誌 114 (臨増) 336 -336 2010年03月 [査読無し][通常論文]
  • 加瀬 諭, 北市 伸義, 大野 重昭 臨床眼科 64 (2) 172 -176 2010年02月
  • Satoru Kase, Wataru Saito, Akari Saito, Shigeaki Ohno JAPANESE JOURNAL OF OPHTHALMOLOGY 54 (1) 109 -110 2010年01月 [査読無し][通常論文]
  • 加瀬 諭, 坂本 泰二 あたらしい眼科 = Journal of the eye 25 (11) 1533 -1535 2008年11月30日 [査読無し][通常論文]
  • Satoru Kase, Narsing A. Rao GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY 246 (2) 323 -323 2008年02月 [査読無し][通常論文]
  • 加瀬 諭, 佐藤 出, 中西 勝也, 安藤 亮, 小原 睦子, 高橋 秀史 札幌社会保険総合病院医誌 = Journal of Sapporo Social Insurance General Hospital (JSSIGH) 16 (1) 13 -18 2007年12月01日 
    翼状片は眼球結膜に連続して発生し、角膜輪部を超えて角膜中央へ進入する増殖組織である。本研究では初発翼状片の病理組織学的所見を解析した。bare-sclera法により切除術を行った8例10眼を検討した。切除した組織をフォルマリン固定、パラフィン胞埋、未染標本作製後、ヘマトキシリンーエオジン染色、PAS染色、マッソントリクローム染色、エラスチカワンギーソン染色を行った。10眼とも上皮は細胞異型のない扁平上皮化生を来した円柱上皮であり、基底層に褐色色素沈着があった。8眼で杯細胞過形成、2眼で嚢胞の形成があった。問質には多数の微小血管が分布し、7眼で上皮内へ微小血管が進入していた。6眼で炎症細胞浸潤が強く、リンパ濾胞様の構造を呈していた。10眼で間質に変性した弾性線維の集塊があった。翼状片の病理組織学的所見は多彩であり、その発生病理に関与するもの、および増殖、進展に伴い検出される所見が混在していることが示唆された。
  • Wataru Saito, Satoru Kase, Naoki Furudate, Shigeaki Ohno ARCHIVES OF OPHTHALMOLOGY 125 (10) 1431 -1433 2007年10月 [査読無し][通常論文]
  • 強い黄斑浮腫と閉塞性網膜血管炎を合併した乳頭血管炎の1症例
    齋藤 理幸, 齋藤 航, 加瀬 諭, 古舘 直樹 眼科臨床医報 101 (9) 966 -967 2007年09月 [査読無し][通常論文]
  • 加瀬 諭, 吉田 和彦, 大野 重昭 日本眼科學会雜誌 = Journal of Japanese Ophthalmological Society 111 (8) 577 -586 2007年08月10日 [査読無し][通常論文]
  • Satoru Kase, Masahiko Yokoi, Wataru Saito, Naoki Furudate, Kazuhiro Ohgami, Mizuki Kitamura, Nobuyoshi Kitaichi, Kazuhiko Yoshida, Manabu Kase, Shigeaki Ohno, Toshimitsu Uede OPHTHALMIC RESEARCH 39 (3) 143 -147 2007年 [査読無し][通常論文]
     
    Purpose: Osteopontin ( OPN) has diverse functions such as cell adhesion, chemoattraction, immunomodulation, and angiogenesis. The aim of this study is to analyze the OPN levels in vitreous fluid obtained from diabetic retinopathy ( DR) and non- DR patients. Methods: Nineteen patients out of 11 with DR and 8 without DR underwent pars plana vitrectomy and vitreous fluid was obtained simultaneously. Two distinct sandwich enzyme- linked immunosorbent assay systems ( systems 1 and 2) were applied, which have been developed in our laboratories to quantify the OPN concentrations in vitreous fluid. Results: The non- thrombin- cleaved full- length OPN levels in the vitreous fluid were 921.63 8 45.38 ng/ ml in DR and 632.80 +/- 83.43 ng/ ml in non- DR using system 1. Also, vitreous thrombin- cleaved and noncleaved OPN levels were increased to 2,109.22 +/- 151.651 and 1,651.13 +/- 229.82 ng/ ml in patients with DR and non- DR using system 2. The vitreous OPN levels were significantly higher in DR than those in non- DR ( p < 0.01 by system 1 and p < 0.05 by system 2). Conclusion: Thrombin- cleaved and noncleaved vitreous OPN levels in patients with DR were increased compared with control subjects, suggesting that OPN plays a potential role in the pathogenesis of diabetic retinal ischemia. Copyright (c) 2007 S. Karger AG, Basel.
  • Satoru Kase, Nobuyoshi Kitaichi, Kenichi Namba, Akiko Miyazaki, Kazuhiko Yoshida, Kenji Ishikura, Masahiro Ikeda, Taiji Nakashima, Shigeaki Ohno American journal of kidney diseases : the official journal of the National Kidney Foundation 48 (6) 935 -41 2006年12月 [査読無し][通常論文]
     
    BACKGROUND: Tubulointerstitial nephritis and uveitis (TINU) syndrome is characterized by a combination of idiopathic acute tubulointerstitial nephritis and uveitis. Krebs von den Lunge-6 (KL-6) is a human glycoprotein secreted by type II alveolar cells in the lung, and its serum levels increase in patients with pneumonia of various causes, as well as ocular sarcoidosis. The aim of the present study is to quantify serum KL-6 levels in patients with TINU syndrome, which has no pulmonary and sarcoid lesions, and elucidate the usefulness of KL-6 for the diagnosis and follow-up of this syndrome. METHODS: Serum and urinary samples were obtained from 17 patients with TINU syndrome and 36 age-matched patients with uveitis from other causes. Sarcoidosis was eliminated because serum KL-6 levels increased during their lung lesion. Serum KL-6 level was determined by using a human KL-6 electrochemiluminescence immunoassay. Formalin-fixed paraffin-embedded renal tissue sections were incubated with anti-KL-6 monoclonal antibody, then examined immunohistochemically. RESULTS: Mean serum KL-6 levels for patients with TINU syndrome and those with uveitis from other causes were 363.35 +/- 51.06 and 213.19 +/- 10.28 U/mL, respectively (P < 0.001). Urinary beta(2)-microglobulin levels of patients with TINU syndrome and uveitis from other causes were 4.06 +/- 1.31 and 0.16 +/- 0.20 mg/L, respectively (P < 0.001). All patients with TINU syndrome showed a simultaneous decrease in serum KL-6 and urinary beta(2)-microglobulin levels after the beginning of treatment. Strong immunoreactivity for KL-6 was observed in renal distal tubules in biopsy tissue of patients with TINU syndrome. CONCLUSION: We show a significant increase in serum KL-6 levels in patients with TINU syndrome, whereas levels were normal in patients with other causes of uveitis without nephritis. Renal distal tubules stained strongly with anti-KL-6 antibody, suggesting that high KL-6 levels may reflect the renal lesion of TINU syndrome. Serum KL-6 may be a potential laboratory parameter for the diagnosis and follow-up of patients with TINU syndrome that could complement urinary beta(2)-microglobulin measurements.
  • Wataru Saito, Akari Saito, Kenichi Namba, Satoru Kase, Masanori Shiratori, Shigeaki Ohno JAPANESE JOURNAL OF OPHTHALMOLOGY 50 (6) 558 -561 2006年11月 [査読無し][通常論文]
  • Kase Satoru, Yoshida Kazuhiko, Osaki Mitsuhiko, Adachi Hironobu, Ito Hisao, Ohno Shigeaki Anticancer Research 26 (6) 4535 -4537 2006年 
    Background: Merkel cell carcinoma (MCC) of the eyelid is a rare malignant solid tumor of the elderly, which demonstrates a large, firm, reddish nodule mimicking an angiomatous lesion. The expression of erythropoietin (Epo) and Epo receptor (EpoR), as well as vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR) and basic fibroblast growth factor (bFGF) were examined in human MCC tissues. Materials and Methods: Three patients diagnosed with MCC of the eyelid underwent surgical excision. Isolated tissues were fixed by 4% paraformaldehyde and then were examined using immunohistochemistry. Results: The carcinoma cells consisted of irregular tumor nests with linear stroma and showed hypercellularity indicated by small round nuclei with several mitoses. While immunoreactivity of Epo was undetectable, an increased expression of EpoR was noted in the carcinoma cells. Cytoplasmic immunoreactivity for EpoR was detected in a variety of carcinoma cells, including mitotic cells. VEGF, VEGFR, and bFGF, other angiogenic factors were not expressed in the MCC tissues. Conclusion: EpoR was highly expressed in MCC of the eyelid, suggesting that the Epo-EpoR pathway plays an important role in the formation of MCC.
  • 加瀬 諭, 吉田 和彦, 齋藤 航 臨床眼科 59 (5) 705 -709 2005年05月
  • 吉田 和彦, 原田 高幸, 原田 知加子, 加瀬 諭, 池田 裕美, 酒井 正春, 西 信三, 今城 純子, 中山 啓子, 永濱 裕康, 中山 敬一, 大野 重昭 日本眼科學会雜誌 107 (11) 678 -686 2003年11月10日 [査読無し][通常論文]

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  • 基本医学研究
    開講年度 : 2021年
    課程区分 : 修士課程
    開講学部 : 医学院
    キーワード : 眼科、眼疾患、視覚
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    開講年度 : 2021年
    課程区分 : 修士課程
    開講学部 : 医学院
    キーワード : 眼科、眼疾患、視覚
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    開講年度 : 2021年
    課程区分 : 博士後期課程
    開講学部 : 医学院
    キーワード : 眼科、眼疾患、視覚
  • 基盤医学研究
    開講年度 : 2021年
    課程区分 : 博士後期課程
    開講学部 : 医学院
    キーワード : 眼科、眼疾患、視覚 Ophthalmology, Ocular diseases, Vision
  • 臨床医学研究
    開講年度 : 2021年
    課程区分 : 博士後期課程
    開講学部 : 医学院
    キーワード : 眼科、眼疾患、視覚
  • 関連臨床医学
    開講年度 : 2021年
    課程区分 : 学士課程
    開講学部 : 歯学部
    キーワード : 関連臨床医学、耳鼻咽喉科学、精神医学、臨床心理学、眼科、皮膚科、産婦人科

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