Fundus autofluorescence imaging in acute posterior multifocal placoid pigment epitheliopathy.
Koichi Yokoi, Kenichi Namba, Daiju Iwata, Kazuomi Mizuuchi, Keitaro Hase, Kayo Suzuki, Ryo Ando, Kiriko Hirooka, Nobuko Sekine, Nobuyoshi Kitaichi, Miki Hiraoka, Susumu Ishida
American journal of ophthalmology case reports, 28, 101732, 101732, 2022年12月, ［国際誌］
英語, PURPOSE: Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is a disease characterized by multiple yellowish-white placoid lesions. Although most lesions resolve spontaneously, some turn into scars and lead to permanent visual dysfunction. In this report, we found suggestive findings in fundus autofluorescence (FAF) that may be useful for distinguishing severe lesions requiring treatment in APMPPE. OBSERVATION: Case 1: A 29-year-old woman was referred to our hospital with multiple yellowish-white placoid lesions on the fundi of both eyes (OU). FAF showed hyperautofluorescence in some of these placoid lesions. Based on the findings of fluorescein angiography, a diagnosis of APMPPE was established, and oral prednisolone (PSL) was initiated, given that some lesions were located in the macula. One week later, exacerbation occurred with the newly developed hyperautofluorescent lesions. Some lesions in the right eye (OD) that were hyperautofluorescent at the first visit became hypoautofluorescent. Afterward, although all hypoautofluorescent lesions persisted, most of the hyperautofluorescent lesions disappeared, so oral PSL could be stopped. Two months later, however, the recurrence occurred along with multiple new placoid lesions. Some lesions located at the macula were hyperautofluorescent on FAF OU, indicating the possibility of becoming scar lesions with hypoautofluorescence. Accordingly, oral PSL was given again. CASE 2: A 47-year-old woman noticed decreased vision OD, and she was referred to us. Multiple yellowish-white placoid lesions were seen in the fundi OU. FAF showed hyperautofluorescence both with and without corresponding hypoautofluorescence in the placoid lesions OU. A diagnosis of APMPPE was established, and oral PSL was initiated. Four months later, some lesions that were hyperautofluorescent at the first visit had turned isoautofluorescent, and some lesions OU became hypoautofluorescent. However, all hypoautofluorescent lesions remained hypoautofluorescent OU. Only some hyperautofluorescent lesions recovered to isoautofluorescence without scars. CONCLUSIONS AND IMPORTANCE: In APMPPE, lesions showing hyperautofluorescence on FAF may change into hypoautofluorescence indicating scar formation. Therefore, the presence of hyperautofluorescent lesions in the macula may be a good indicator of the need for intensive corticosteroid treatments to avoid leaving hypoautofluorescent scars that are related to irreversible visual dysfunction.

Placental growth factor stabilizes VEGF receptor-2 protein in retinal pigment epithelial cells by downregulating glycogen synthase kinase 3 activity.
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, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

RESTORATION PROCESS OF THE OUTER RETINAL LAYERS AFTER SURGICAL MACULAR HOLE CLOSURE.
Masanori Iwasaki, Ryo Ando, Shuichiro Aoki, Hirotomo Miyamoto
Retina (Philadelphia, Pa.), 42, 2, 313, 320, 2022年02月01日, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: To investigate the interrelationship among the outer retinal layers after macular hole surgery and elucidate the restoration process. METHODS: This retrospective observational study included 50 eyes of 47 consecutive patients with closed macular holes in the first vitrectomy. Optical coherence tomography was obtained before surgery; at 1, 3, and 6 months postsurgery; and at the last visit. The complete continuous layer rate and mean defect length were evaluated for the outer nuclear layer (ONL), external limiting membrane (ELM), and ellipsoid zone (EZ). RESULTS: At all postoperative visits, the complete continuous layer rate was in the descending order of ELM, ONL, and EZ and the mean defect length was in the ascending order of ELM, ONL, and EZ. External limiting membrane was necessary for ONL restoration. External limiting membrane and ONL were necessary for EZ restoration. Hyperreflective protrusions were observed from the area lacking ELM into the subretinal space after surgery. Ellipsoid zone was not formed in coexistence with the hyperreflective protrusions. Intermediate reflective protrusions appeared under the ONL plus ELM after surgery and were eventually replaced by EZ. CONCLUSION: Restoration of the outer retinal layers after surgical macular hole closure occurs in the order of ELM, ONL, and EZ.

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
日本語

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
日本語

A Case of Recurrent Painful Ophthalmoplegic Neuropathy in a Child
Ai Sakuma, Hideaki Shiraishi, Yasuhiro Shinmei, Ryo Ando, Kiriko Hirooka, Tomoko Shiroeda, Kayo Suzuki, Kayoko Nakamura, Shinki Chin, Susumu Ishida
Neuro-Ophthalmology Japan, 37, 1, 51, 57, Neuro-Ophthalmology Society of Japan, 2020年03月25日
日本語, 研究論文（学術雑誌）, Recurrent painful ophthalmoplegic neuropathy（RPON）, previously known as ophthalmoplegic migraine, is a rare condition that manifests as headache and ophthalmoplegia. The involved cranial nerve shows gadolinium enhancement or thickening on magnetic resonance imaging（MRI）in the acute phase. Herein, we report a case of RPON in a 4-year-old boy with recurrent episodes of oculomotor palsy for 8 years. He complained of left ptosis and presented with exotropia and hypertropia in the left eye at the first visit to our clinic. His left eye had limitations of adduction, supraduction, and infraduction. He had isocoria with prompt reaction to light. Contrast-enhanced MRI revealed enhancement and thickening of the left oculomotor nerve. The patient had experienced a similar episode 2 years before, which had resolved completely with steroid therapy
therefore, the same treatment was chosen, and it resolved the symptoms. He experienced ten recurrences in the following 8 years. On MRI for each recurrence, enhancement and thickening of the left oculomotor nerve was observed. Although the enhancement improved with the use of steroids, the thickening remained unchanged. The left oculomotor palsy showed complete recovery with the use of steroids, without any residual neurological deficits, at all recurrences.

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
日本語

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
日本語

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
日本語, 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］
日本語, 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)

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
日本語

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］
日本語

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
日本語

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
日本語

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
日本語

Clinical features of Japanese patients with anti-α-enolase antibody-positive autoimmune retinopathy: Novel subtype of multiple drusen.
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］, ［国際誌］
英語, 研究論文（学術雑誌）, 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.

【眼内血管新生疾患の病態と治療-加齢黄斑変性と糖尿病網膜症】加齢黄斑変性 滲出型加齢黄斑変性に対する併用療法
安藤 亮, 野田 航介
医学のあゆみ, 266, 12, 908, 913, 医歯薬出版(株), 2018年09月
日本語, 以前、有効な治療法が存在しなかった加齢黄斑変性(AMD)に対して光線力学療法が臨床導入された時、画期的な治療方法として注目を集めた。病的新生血管へ選択的に取り込まれたベルテポルフィンが照射レーザーによって活性酸素を生じ、血管を閉塞させる。しかし、正常組織への影響はゼロではなく、治療後に起こる虚血や炎症によって再発や合併症を生じることが少なくなかった。そのため、その後に出現した抗血管内皮増殖因子(VEGF)療法に主役の座を奪われてしまったという経緯がある。しかし、2017年にAMDの特殊型である(しかしアジア人では有病率の高い)ポリープ状脈絡膜血管症(PCV)に対する大規模ランダム化臨床試験の結果が報告され、光線力学療法は大きく見直されることとなった。抗VEGF療法単独と比較して、光線力学療法と抗VEGF療法の併用療法が視力改善、治療回数などにおいて優位性を示したのである。今後は併用療法についての研究が多くなされ、最適化されていくと考えられる。また、併用療法にステロイドを加えたトリプル療法も選択肢となりうる。(著者抄録)

Soluble Vascular Adhesion Protein-1 Mediates Spermine Oxidation as Semicarbazide-Sensitive Amine Oxidase: Possible Role in Proliferative Diabetic Retinopathy
Miyuki Murata, Kousuke Noda, Akiko Kawasaki, Shiho Yoshida, Yoko Dong, Michiyuki Saito, Zhenyu Dong, Ryo Ando, Shohei Mori, Wataru Saito, Atsuhiro Kanda, Susumu Ishida
Current Eye Research, 42, 12, 1674, 1683, Taylor and Francis Ltd, 2017年12月02日, ［査読有り］
英語, 研究論文（学術雑誌）, Purpose/Aim of the study: To explore the possible role of vascular adhesion protein-1 (VAP-1) via its enzymatic function as a semicarbazide-sensitive amine oxidase (SSAO) in the pathogenesis of proliferative diabetic retinopathy (PDR). Materials and Methods: The levels of soluble VAP-1/SSAO and the unsaturated aldehyde acrolein (ACR)-conjugated protein, Nε-(3-formyl-3, 4-dehydropiperidino) lysine adduct (FDP-Lys), were measured in vitreous fluid samples of PDR and non-diabetic patients using ELISA. Recombinant human VAP-1/SSAO (rhVAP-1/SSAO) was incubated with spermine, with or without semicarbazide or RTU-1096 (a specific inhibitor for VAP-1/SSAO). Immunofluorescence assays were performed to assess the localization of VAP-1/SSAO and FDP-Lys in fibrovascular tissues from patients with PDR. The impact of ACR on cultured retinal capillary endothelial cells was assessed using a cell viability assay and total glutathione (GSH) measurements. Results: The levels of sVAP-1/SSAO and FDP-Lys were elevated in the vitreous fluid of patients with PDR. Incubation of rhVAP-1 with spermine resulted in the generation of hydrogen peroxide and FDP-Lys and the production was inhibited by semicarbazide and RTU-1096. In fibrovascular tissues, FDP-Lys and VAP-1/SSAO were present in endothelial cells. ACR stimulation reduced GSH levels in the cultured endothelial cells in a dose-dependent manner and caused cellular toxicity. Conclusions: Our results indicate the pathological role of sVAP-1/SSAO to generate hydrogen peroxide and toxic aldehyde ACR, both of which are associated with oxidative stress, as a consequence of spermine oxidation in eyes with PDR.

Blood flow velocity and thickness of the choroid in a patient with chorioretinopathy associated with ocular blunt trauma
Yuri Ishikawa, Yuki Hashimoto, Wataru Saito, Ryo Ando, Susumu Ishida
BMC OPHTHALMOLOGY, 17, 1, 86, BIOMED CENTRAL LTD, 2017年06月, ［査読有り］
英語, 研究論文（学術雑誌）, Background: Choroidal circulation hemodynamics in eyes with ocular blunt trauma has not been quantitatively examined yet. We quantitatively examined changes in choroidal blood flow velocity and thickness at the lesion site using laser speckle flowgraphy (LSFG) and enhanced depth imaging optical coherence tomography (EDI-OCT) in a patient with chorioretinopathy associated with ocular blunt trauma.
Case presentation: A 13-year-old boy developed a chorioretinal lesion with pigmentation extending from the optic disc to the superotemporal side in the right eye after ocular blunt trauma. The patient's best-corrected visual acuity (BCVA) was 0.2 in the right eye. Indocyanine green angiography showed hypofluorescence from the initial phase, with a decrease of mean blur rate (MBR) on LSFG color map, which corresponded to the chorioretinal lesion. The BCVA and foveal outer retinal morphologic abnormality spontaneously improved during follow-up. MBR and choroidal thickness increased by 23-31% and 13-17 mu m at the lesion site and by 11-22% and 33-42 ae m at the fovea, respectively, during the 6-month follow-up period after baseline measurements in the affected eye. In contrast, these parameters showed little or no changes at the normal retinal site in the affected eye and the fovea in the fellow eye.
Conclusions: Current data revealed that both blood flow velocity and thickness in the choroid at the lesion site decreased in the acute stage and subsequently increased together with improvements in visual function and outer retinal morphology. These results suggest that LSFG and EDI-OCT may be useful indices that can noninvasively evaluate activity of choroidal involvement in ocular blunt trauma-associated chorioretinopathy.

Clinical and histological evaluation of large macular hole surgery using the inverted internal limiting membrane flap technique
Satoru Kase, Wataru Saito, Shohei Mori, Michiyuki Saito, Ryo Aando, Zhenyu Dong, Tomohiro Suzuki, Kousuke Noda, Susumu Ishida
Clinical Ophthalmology, 11, 9, 14, Dove Medical Press Ltd, 2017年01月01日, ［査読有り］
英語, 研究論文（学術雑誌）, 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.

Effect of geranylgeranylacetone on the protection of retinal ganglion cells in a mouse model of normal tension glaucoma.
Zhenyu Dong, Yasuhiro Shinmei, Yoko Dong, Saori Inafuku, Junichi Fukuhara, Ryo Ando, Nobuyoshi Kitaichi, Atsuhiro Kanda, Kohichi Tanaka, Kousuke Noda, Takayuki Harada, Shinki Chin, Susumu Ishida
Heliyon, 2, 10, e00191, 2016年10月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Glaucoma is characterized by axonal degeneration of retinal ganglion cells (RGCs) and apoptotic death of their cell bodies, and lowering intraocular pressure is associated with an attenuation of progressive optic nerve damage. Nevertheless, intraocular pressure (IOP) reduction alone was not enough to inhibit the progression of disease, which suggests the contribution of other factors to the glaucoma pathogenesis. In this study, we investigated the cytoprotective effect of geranylgeranylacetone (GGA) on RGCs degeneration using a normal tension glaucoma (NTG) mouse model, which lacks glutamate/aspartate transporter (GLAST) and demonstrates spontaneous RGC and optic nerve degeneration without elevated intraocular pressure (IOP). Three-week-old GLAST+/- mice were given oral administration of GGA at 100, 300, or 600 mg/kg/day or vehicle alone, and littermate control mice were given vehicle alone for 14 days, respectively. At 5 weeks after birth, the number of RGCs was counted in paraffin sections of retinal tissues stained with hematoxylin and eosin. In addition, retrograde labeling technique was also used to quantify the number of RGC. Expression and localization of heat shock protein 70 (HSP70) in retinas were evaluated by reverse transcription polymerase chain reaction and immunohistochemistry, respectively. Activities of caspase-9 and -3 in retinas were also assessed. The number of RGCs of GLAST+/- mice significantly decreased, as compared to that of control mice. RGC loss was significantly suppressed by administration of GGA at 600 mg/kg/day, compared with vehicle alone. Following GGA administration, HSP70 was significantly upregulated together with reduction in the activities of caspase-9 and -3. Our studies highlight HSP70 induction in the retina is available to suppress RGC degeneration, and thus GGA may be applicable for NTG as a promising therapy.

Phosphorylation of alphaB-crystallin in epiretinal membrane of human proliferative diabetic retinopathy
Yoko Dong, Zhenyu Dong, Satoru Kase, Ryo Ando, Junichi Fukuhara, Satoshi Kinoshita, Saori Inafuku, Yoshiaki Tagawa, Erdal Tan Ishizuka, Wataru Saito, Miyuki Murata, Atsuhiro Kanda, Kousuke Noda, Susumu Ishida
INTERNATIONAL JOURNAL OF OPHTHALMOLOGY, 9, 8, 1100, 1105, IJO PRESS, 2016年08月, ［査読有り］
英語, 研究論文（学術雑誌）, AIM: To examine phosphorylation of alphaB-crystallin (p-alpha BC), a vascular endothelial growth factor (VEGF) chaperone, and immunohistochemically investigate relationship between p-alpha BC, 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-alpha BC, VEGF, CD31, and p-p38 MAPK antibodies.
RESULTS: Immunoreactivity for p-alpha BC 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-alpha BC was detected in the CD31-positive endothelial cells, and co-localized with VEGF and p-p38 MAPK in PDR membranes. Immunoreactivity for p-alpha BC, however, was undetectable in endothelial cells of the normal retinas, where p-p38 MAPK immunoreactivity was less marked than PDR membranes.
CONCLUSION: Phosphorylation of alpha BC, 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.

Effect of horizontal transposition of vertical rectus muscle for treatment of acquired trochlear nerve palsy　　　　　　　　　　　　　　　
Sayaka Ishigaki, Yasuhiro Shinmei, Ryo Ando, Mayo Nozaki, Ayako Mizoguchi, Tomoko Abe, Shinki Chin, Susumo Ishida
Folia Japonica de Ophthalmologica Clinica, 9, 4, 323, 327, Association of Folia Ophthalmologica Japonica, 2016年04月01日
日本語, 研究論文（学術雑誌）, Purpose : The aim of this study was to examine the effects of horizontal transposition of the vertical rectus muscles performed for excyclotropia caused by acquired trochlear nerve palsy. Methods : The records of patients diagnosed with acquired trochlear nerve palsy were evaluated. Five patients underwent horizontal transposition surgery of the vertical rectus muscles. All surgeries were performed on paretic eyes (nasal transposition of the inferior rectus muscle with resection for 3 cases, temporal transposition of the superior rectus muscle with recession for 1 case, and nasal transposition of the inferior rectus muscle alone for 1 case). Results : The extent of cyclodeviation and vertical deviation was improved postoperatively from 7.5 ±1.9° to 2.8 ±2.2° and from 5.6 ±3.3° to 3.8 ±1.5°, respectively. The average effect of horizontal transposition of the vertical rectus muscles for cyclodeviation was 4.7 ± 1.7° per one tendon width, while for vertical deviation it was 0.4 ±1.0° per 1 mm. Conclusions : Ipsilateral horizontal transposition of the vertical rectus muscles is effective for treatment of excyclotorsion due to acquired trochlear nerve palsy.

Amelioration of experimental autoimmune uveoretinitis by inhibition of glyceraldehyde-derived advanced glycation end-product formation
Zhenyu Dong, Daiju Iwata, Nobuyoshi Kitaichi, Masayoshi Takeuchi, Masashi Sato, Noriko Endo, Kazuya Iwabuchi, Ryo Ando, Junichi Fukuhara, Satoshi Kinoshita, Anton Lennikov, Mizuki Kitamura, Kazuomi Mizuuchi, Atsuhiro Kanda, Kousuke Noda, Kenichi Namba, Sho-Ichi Yamagishi, Shigeaki Ohno, Susumu Ishida
JOURNAL OF LEUKOCYTE BIOLOGY, 96, 6, 1077, 1085, FEDERATION AMER SOC EXP BIOL, 2014年12月, ［査読有り］
英語, 研究論文（学術雑誌）, Formation of glyceraldehyde-derived advanced glycation endoproducts contributes to the pathogenesis of endogenous uvetitis in human and animals. AGEs are permanently modified macromolecule derivatives that form through nonenzymatic glycation of amino groups of proteins. Glycer-AGEs are highly toxic and play an important role in the pathogenesis of chronic inflammatory diseases. However, the contribution of glycer-AGEs to the pathogenesis of uveitis is unclear. In this study, we measured serum levels of glycer-AGEs in 100 patients with endogenous uveitis (22 with HLA-B27-associated uveitis, 20 with VKH disease, 14 with Behcet's disease, and 44 with sarcoidosis) and 33 healthy volunteers. We then examined the effect of the AGE inhibitor in a mouse model of human endogenous uveitis (EAU) by continuous oral administration of pyridoxamine at 200 or 400 mg/kg/day. Regardless of the etiology, serum glycer-AGE levels were significantly higher in patients with uveitis than in healthy subjects. Treatment with 400 mg/kg pyridoxamine significantly reduced the clinical and histological severity of EAU and was accompanied by a significant decrease in serum and retinal glycer-AGE levels and suppression of translocation of NF-B p65 into the nucleus of retinal cells. Serum glycer-AGE levels may therefore serve as a biomarker of human uveitis, as well as systemic inflammation, and may contribute to the progression of uveitis, including diabetic iritis, via the activation of NF-B.

Genistein attenuates choroidal neovascularization
Satoshi Kinoshita, Kousuke Noda, Yoshiaki Tagawa, Saori Inafuku, Yoko Dong, Junichi Fukuhara, Zhenyu Dong, Ryo Ando, Atsuhiro Kanda, Susumu Ishida
JOURNAL OF NUTRITIONAL BIOCHEMISTRY, 25, 11, 1177, 1182, ELSEVIER SCIENCE INC, 2014年11月, ［査読有り］
英語, 研究論文（学術雑誌）, Genistein is a dietary-derived flavonoid abundantly present in soybeans and known to possess various biological effects including anti-inflammation and anti-angiogenic activity. To investigate the effects of genistein on intraocular neovascularization, we used an animal model of laser-induced choroidal neovascularization (CNV). Male C57BL/6J mice were treated in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. CNV was induced by laser photocoagulation. The animals were fed a mixture diet containing 0.5% genistein or a control diet ad libitum for 7 days before laser photocoagulation and the treatment was continued until the end of the study. Seven days after laser injury, the size of CNV lesions was quantified. Retinal pigment epithelium (RPE)-choroid complex was also harvested 1 or 3 days after laser injury and the level of monocyte chemoattractant protein (MCP)-1, intercellular adhesion molecule (ICAM)-1, and matrix metalloproteinase (MMP)-9 were measured by enzyme-linked immunosorbent assay. Expression levels of Ets-1 and F4/80 were examined by real-time PCR. A significant decrease in CNV size was observed in animals treated with genistein (15441.9+/-1511.8 mu m(2)) compared to control mice (21074.0+/-1940.7 mu m(2), P<.05). Genistein significantly reduced the protein level of MCP-1, ICAM-1, and MMP-9 in the RPE-choroid complex (P<.05). In addition, genistein suppressed the expression levels of Ets-1 and F4/80 (P<.05). The current data indicate the anti-angiogenic property of genistein during CNV formation. (C) 2014 Elsevier Inc. All rights reserved.

Decreased proteasomal activity causes photoreceptor degeneration in mice
Ryo Ando, Kousuke Noda, Utano Tomaru, Mamoru Kamoshita, Yoko Ozawa, Shoji Notomi, Toshio Hisatomi, Mika Noda, Atsuhiro Kanda, Tatsuro Ishibashi, Masanori Kasahara, Susumu Ishida
Investigative Ophthalmology and Visual Science, 55, 7, 4682, 4690, Association for Research in Vision and Ophthalmology Inc., 2014年07月03日, ［査読有り］
英語, 研究論文（学術雑誌）, Purpose: To study the retinal degeneration caused by decreased proteasomal activity in β5t transgenic (β5t-Tg) mice, an animal model of senescence acceleration. Methods: β5t-Tg mice and age-matched littermate control (WT) mice were used. Proteasomal activities and protein level of poly-ubiquitinated protein in retinal extracts were quantified. Fundus images of β5t-Tg mice were taken and their features were assessed. For histologic evaluation, the thicknesses of inner nuclear layer (INL), outer nuclear layer (ONL), and photoreceptor outer segment (OS) were measured. For functional analysis, ERG was recorded under scotopic and photopic illumination conditions. Immunofluorescence (IF) staining and TUNEL were performed to investigate the mechanism of photoreceptor degeneration. Results: Chymotrypsin-like activity was partially suppressed in retinal tissues of β5t-Tg mice. Retinal degenerative changes with arterial attenuation were present in β5t-Tg, but not in WT mice. Inner nuclear layer thickness showed no significant change between β5t-Tg and WT mice at 1, 3, 6, and 9 months of age. By contrast, thicknesses of ONL and OS in β5t-Tg mice were significantly decreased at 3, 6, and 9 months compared with those in WT mice. Electroretinograms showed decrease of scotopic a-wave amplitude in β5t-Tg mice. The number of TUNEL-positive cells in ONL were significantly increased in β5t-Tg mice and colocalized with apoptosis-inducing factor, but not with cleaved caspase-3 and -9, indicating that the photoreceptor cell death was induced via a caspase-independent pathway. Conclusions: The current data showed that impaired proteasomal function causes photoreceptor degeneration. © 2014 The Association for Research in Vision and Ophthalmology, Inc.

Expression of Vascular Endothelial Growth Factor in Human Ocular Adnexal Lymphoma
Satoshi Kinoshita, Satoru Kase, Ryo Ando, Zhenyu Dong, Junichi Fukuhara, Yoko Dong, Saori Inafuku, Kousuke Noda, Mika Noda, Atsuhiro Kanda, Susumu Ishida
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 55, 6, 3461, 3467, ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2014年06月, ［査読有り］
英語, 研究論文（学術雑誌）, PURPOSE. To examine the expression of VEGF in extranodal marginal zone B-cell lymphoma (EMZL) and reactive lymphoid hyperplasia (RLH) of human ocular adnexa, and analyze the correlation with the intratumoral microvessel density (MVD).
METHODS. Twenty-two EMZL and 16 RLH tissues were examined in this study. Paraformaldehyde-fixed, paraffin-embedded tissue sections were processed for immunohistochemistry with antibodies against VEGF and CD20. Vascular endothelial growth factor expression was analyzed using the ELISA and RT-PCR in the EMZL tissues. Microvessel density was determined based on the immunoreactivity for anti-CD34 antibody.
RESULTS. Vascular endothelial growth factor immunoreactivity was detected in the cytoplasm of lymphoid cells in EMZL and RLH. ELISA and RT-PCR confirmed VEGF protein and mRNA expressions in the EMZL tissue, respectively. Vascular endothelial growth factor-immunopositive rate in B-cells was significantly higher in 12 conjunctival EMZLs than four RLHs (P < 0.01) and 10 orbital EMZLs than 12 RLHs (P < 0.05). The MVD showed a significant positive correlation with the VEGF-immunopositive rate in conjunctival and orbital EMZLs.
CONCLUSIONS. This study demonstrated increased VEGF expression in human conjunctival and orbital EMZL compared with that in RLH, suggesting that VEGF plays a significant role in the pathogenesis and tumor angiogenesis of ocular adnexal lymphoma.

Aqueous humour levels of placental growth factor in diabetic retinopathy
Ryo Ando, Kousuke Noda, Shiho Namba, Wataru Saito, Atsuhiro Kanda, Susumu Ishida
ACTA OPHTHALMOLOGICA, 92, 3, E245, E246, WILEY-BLACKWELL, 2014年05月, ［査読有り］
英語

Amelioration of endotoxin-induced uveitis treated with the sea urchin pigment echinochrome in rats
Anton Lennikov, Nobuyoshi Kitaichi, Kousuke Noda, Kazuomi Mizuuchi, Ryo Ando, Zhenyu Dong, Junichi Fukuhara, Satoshi Kinoshita, Kenichi Namba, Shigeaki Ohno, Susumu Ishida
MOLECULAR VISION, 20, 171, 177, MOLECULAR VISION, 2014年02月, ［査読有り］
英語, 研究論文（学術雑誌）, Purpose: Echinochrome is a pigment present in the shells and spines of sea urchins. It has been reported to have several biologic protective effects, including in experimental models of myocardial ischemia/reperfusion injury, for which the proposed mechanisms are scavenging reactive oxygen species (ROS) and chelating iron. Endotoxin-induced uveitis (EIU) is an animal model of acute anterior segment intraocular inflammation that is induced by the injection of lipopolysaccharide (LPS). In this study, the therapeutic effect of echinochrome was examined in uveitis using the EIU model.
Methods: EIU was induced in Lewis rats via 200 mu g subcutaneous injections of LPS from Escherichia coli. Echinochrome was administered intravenously in 10, 1, or 0.1 mg/kg doses suspended in PBS (controls were injected with PBS only). Twenty-four hours after LPS injection, the number of infiltrating cells and the protein concentration in aqueous humor were determined. Aqueous tumor necrosis factor alpha (TNF-alpha) concentration was quantified with enzyme-linked immunosorbent assay, eyes were stained with nuclear factor (NF) kappa B antibodies, and ROS production was determined by dihydroethidium staining in fresh frozen samples.
Results: The number of inflammatory aqueous cells and protein levels were lower in the groups treated with 10 and 1 mg/kg of echinochrome than in the untreated LPS group (p<0.01). Treatment with 10 and 1 mg/kg of echinochrome significantly reduced TNF-alpha concentrations in aqueous humor (p<0.01). The numbers of NF kappa B-positive cells and ROS signals were also reduced by echinochrome administration (p<0.05).
Conclusions: Echinochrome ameliorated intraocular inflammation caused by EIU by reducing ROS production, thereby also decreasing the expression of NF kappa B and TNF-alpha. As a natural pigment, echinochrome may therefore be a promising candidate for the safe treatment of intraocular inflammation. The use of sea urchin shells and spines in health foods and medical products is thus both economically and environmentally meaningful.

Expression of αB-crystallin and vascular endothelial growth factor in conjunctival squamous cell carcinoma.
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, INT INST ANTICANCER RESEARCH, 2013年09月, ［査読有り］
英語, 研究論文（学術雑誌）, Aim: To examine the expression of alpha B-crystallin and vascular endothelial growth factor (VEGF) in conjunctival squamous cell carcinoma (CSCC). Materials and Methods: Seven CSCCs and three normal conjunctivas that were surgically excised were studied. Paraformaldehyde-fixed, paraffin-embedded tissue sections were processed for immunohistochemistry with antibodies against alpha B-crystallin, its phosphorylated forms, and VEGF. In vitro experiments were conducted to investigate the effects of mitomycin C (MMC) treatment on the expression of alpha B-crystallin and VEGF secretion. Results: alpha B-Crystallin and VEGF were strongly expressed in CSCCs compared to normal conjunctivas. alpha B-Crystallin immunoreactivity was co-localized with that for VEGF in CSCCs, whereas these signals were reduced in CSCC tissues treated with MMC before excision. MMC treatment suppressed the alpha B-crystallin expression and VEGF secretion in cultured conjunctival cells in a dose-dependent manner. Conclusion: This study demonstrated alpha B-crystallin and VEGF expressions in human CSCCs, which may play a role in the pathogenesis. alpha B-Crystallin expression, and VEGF secretion were reduced by MMC, indicating a novel therapeutic mechanism in MMC treatment for human CSCC.

Specific inhibition of serine/arginine-rich protein kinase attenuates choroidal neovascularization
Zhenyu Dong, Kousuke Noda, Atsuhiro Kanda, Junichi Fukuhara, Ryo Ando, Miyuki Murata, Wataru Saito, Masatoshi Hagiwara, Susumu Ishida
MOLECULAR VISION, 19, 536, 543, MOLECULAR VISION, 2013年03月, ［査読有り］
英語, 研究論文（学術雑誌）, Purpose: To investigate the applicability of serine/arginine-rich protein kinase (SRPK)-specific inhibitor, SRPIN340, for attenuation of choroidal neovascularization (CNV) formation using a mouse model.
Methods: Laser photocoagulation was performed to induce CNV in C57BL/'6J mice, followed by intravitreal injection of SRPIN340 or vehicle. Seven days after the treatment, the CNV size was evaluated using a flatmount technique. Protein levels of vascular endothelial growth factor (VEGF) and inflammation-associated molecules, such as monocyte chemoattractant protein (MCP)-1 and intercellular adhesion molecule (ICAM)-1, in the retinal pigment epithelium-choroid complex were measured with enzyme-linked immunosorbent assay. Expression levels of total Vegf, exon 8a-containing Vegf isoforms, and F4/80 (a specific marker for macrophage) were assessed using real-time PCR.
Results: SRPIN340 inhibited CNV formation in a dose-dependent manner. Compared with the vehicle, SRPIN340 significantly decreased the protein levels of VEGF, MCP-1, ICAM-1, and consequently inhibited macrophage infiltration. Furthermore, SRPIN340 suppressed the gene expression levels of total Vegf and exon 8a-containing Vegf isoforms.
Conclusions: SRPIN340, a specific inhibitor of SRPK, suppressed Vegf expression and attenuated CNV formation. Our data suggest the possibility that SRPIN340 is applicable for neovascular age-related macular degeneration as a novel chemical therapeutics.

Expression of vascular endothelial growth factor C in human pterygium
Junichi Fukuhara, Satoru Kase, Tsutomu Ohashi, Ryo Ando, Zhenyu Dong, Kousuke Noda, Takeshi Ohguchi, Atsuhiro Kanda, Susumu Ishida
Histochemistry and Cell Biology, 139, 2, 381, 389, 2013年02月, ［査読有り］
英語, 研究論文（学術雑誌）, 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. 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 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 and were evaluated using immunohistochemistry. 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. 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. © 2012 Springer-Verlag.

Tissue Kallikrein Attenuates Choroidal Neovascularization via Cleavage of Vascular Endothelial Growth Factor
Junichi Fukuhara, Kousuke Noda, Miyuki Murata, Shiho Namba, Satoshi Kinoshita, Zhenyu Dong, Ryo Ando, Anton Lennikov, Atsuhiro Kanda, Susumu Ishida
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 54, 1, 274, 279, ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2013年01月, ［査読有り］
英語, 研究論文（学術雑誌）, PURPOSE. To investigate the antiangiogenic properties of tissue kallikrein in a murine model of laser-induced choroidal neovascularization (CNV).
METHODS. CNV was induced in male C57BL/6J mice by laser photocoagulation. The animals received daily subcutaneous injections of tissue kallikrein (50 lg/kg) or vehicle control for 2 days before the laser photocoagulation, and this treatment continued until sample collection. Seven days after laser injury, the CNV size was quantified. The levels of monocyte chemoattractant protein (MCP)-1, intercellular adhesion molecule (ICAM)-1, and interleukin (IL)-6 were assessed by enzyme-linked immunosorbent assay 3 days after laser injury. Cleavage of mouse VEGF with tissue kallikrein was assessed in vivo and in vitro. The protein levels of bradykinin were assessed in the RPE-choroid complexes and hearts.
RESULTS. A significant decrease in CNV size was observed in animals treated with tissue kallikrein (27,168.3 +/- 2432.2 mu m(2)) compared with vehicle-treated controls (36,374.6 +/- 3204.1 mu m(2), P < 0.05). Tissue kallikrein treatment significantly reduced MCP-1, ICAM-1, and IL-6 levels in RPE-choroid complexes. Furthermore, immunoblotting showed the bands, presumably corresponding to the fragmented VEGF(164) protein, in the samples of both mouse VEGF preincubated with tissue kallikrein and RPE-choroid complexes obtained from animals treated with tissue kallikrein. In addition, bradykinin was unchanged in the RPE-choroid complexes of animals treated with tissue kallikrein, whereas the level of bradykinin was increased in the heart obtained from these experimental animals.
CONCLUSIONS. The current data indicate that kallikrein exhibits antiangiogenic properties by cleaving VEGF164 in a laser-induced CNV model. (Invest Ophthalmol Vis Sci. 2013; 54: 274279) DOI: 10.1167/iovs.12-10512

Amelioration of endotoxin-induced uveitis treated with an IκB kinase β inhibitor in rats.
Lennikov A, Kitaichi N, Noda K, Ando R, Dong Z, Fukuhara J, Kinoshita S, Namba K, Mizutani M, Fujikawa T, Itai A, Ohno S, Ishida S
Molecular vision, 18, 267-70, 2586, 2597, MOLECULAR VISION, 2012年10月, ［査読有り］
英語, 研究論文（学術雑誌）, Purpose: Endotoxin-induced uveitis (EIU) is an animal model for acute ocular inflammation. Several substances play major roles in the development of inflammatory changes in EIU, including tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, and IL-6. These inflammatory cytokines trigger the degradation of I kappa B by activating I kappa B kinases (IKKs). Released nuclear factor kappaB (NF kappa B) subsequently translocates to the nucleus, where NF kappa B expresses its proinflammatory function. IMD-0354, N-(3,5-Bis-trifluoromethylphenyl)-5-chloro-2-hydroxybenzamide, selectively inhibits IKK beta, particularly when induced by proinflammatory cytokines, such as TNF-alpha and IL-1 beta. In the present study, we examined whether IKK beta inhibition has therapeutic effects on EIU by using IMD-0354 and its prodrug IMD-1041.
Methods: Six-week-old male Lewis rats were used. EIU was induced with subcutaneous injections of 200 mu g of lipopolysaccharide (LPS) from Escherichia coli that had been diluted in 0.1 ml of phosphate-buffered saline. IMD-0354 was administered intraperitoneally at 30, 10, 3, or 0 mg/kg, suspended in 1.0 ml of 0.5% carboxymethyl cellulose sodium. The prodrug IMD-1041 (100 mg/kg) was also administered orally. The rats were euthanized 24 h after LPS injection, and EIU severity was evaluated histologically. The number of infiltrating cells and the protein, TNF-alpha, and monocyte chemoattractant protein-1 (MCP-1) concentrations in the aqueous humor were determined. TNF-alpha and MCP-1 concentrations were quantified with enzyme-linked immunosorbent assay. Eye sections were also stained with anti-NF kappa B and phosphorylated I-kappa B alpha antibodies.
Results: The number of infiltrating cells in aqueous humor was 53.6 +/- 9.8x10(5), 72.5 +/- 17.0x10(5), 127.25 +/- 32.0x10(5), and 132.0 +/- 25.0x10(5) cells/ml in rats treated with 30, 10, 3, or 0 mg/kg of IMD-0354, respectively. The total protein concentrations of aqueous humor were 92.6 +/- 3.1 mg/ml, 101.5 +/- 6.8 mg/ml, 112.6 +/- 1.9 mg/ml, and 117.33 +/- 1.8 mg/ml in rats treated with 30, 10, 3, and 0 mg/kg of IMD-0354, respectively. Infiltrating cells and protein concentrations were significantly decreased by treatment with IMD-0354 (p < 0.01). IMD-0354 treatment significantly reduced the concentration of TNF-alpha (p < 0.05) and MCP-1 (p < 0.01) in aqueous humor. The number of NF kappa B positive nuclei was reduced when treated with IMD-0354. Furthermore, IMD-0354-treated EIU rats showed only background levels of phosphorylated I-kappa B alpha; however, it was strongly expressed in the iris-ciliary body cell cytoplasm of the IMD-0354 untreated EIU rats. Oral administration of IMD-1041 also decreased the cell number (p < 0.01) and protein concentration (p < 0.05) of aqueous humor in EIU.
Conclusions: Acute uveitis was ameliorated by inhibition of IKK beta in rats. IMD-0354 and its prodrug IMD-1041 seem to be promising candidates for treating intraocular inflammation/uveitis.

ALPHAB-CRYSTALLIN EXPRESSION IN EPIRETINAL MEMBRANE OF HUMAN PROLIFERATIVE DIABETIC RETINOPATHY
Zhenyu Dong, Satoru Kase, Ryo Ando, Junichi Fukuhara, Wataru Saito, Atsuhiro Kanda, Miyuki Murata, Kousuke Noda, Susumu Ishida
RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES, 32, 6, 1190, 1196, LIPPINCOTT WILLIAMS & WILKINS, 2012年06月, ［査読有り］
英語, 研究論文（学術雑誌）, 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. RETINA 32:1190-1196, 2012

Amelioration of ultraviolet-induced photokeratitis in mice treated with astaxanthin eye drops
Anton Lennikov, Nobuyoshi Kitaichi, Risa Fukase, Miyuki Murata, Kousuke Noda, Ryo Ando, Takeshi Ohguchi, Tetsuya Kawakita, Shigeaki Ohno, Susumu Ishida
MOLECULAR VISION, 18, 49, 455, 464, MOLECULAR VISION, 2012年02月, ［査読有り］
英語, 研究論文（学術雑誌）, Purpose: Ultraviolet (UV) acts as low-dose ionizing radiation. Acute UVB exposure causes photokeratitis and induces apoptosis in corneal cells. Astaxanthin (AST) is a carotenoid, present in seafood, that has potential clinical applications due to its high antioxidant activity. In the present study, we examined whether topical administration of AST has preventive and therapeutic effects on UV-photokeratitis in mice.
Methods: C57BL/6 mice were administered with AST diluted in polyethylene glycol (PEG) in instillation form (15 mu l) to the right eye. Left eyes were given vehicle alone as controls. Immediately after the instillation, the mice, under anesthesia, were irradiated with UVB at a dose of 400 mJ/cm(2). Eyeballs were collected 24 h after irradiation and stained with H&E and TUNEL. In an in vitro study, mouse corneal epithelial (TKE2) cells were cultured with AST before UV exposure to quantify the UV-derived cytotoxicity.
Results: UVB exposure induced cell death and thinning of the corneal epithelium. However, the epithelium was morphologically well preserved after irradiation in AST-treated corneas. Irradiated corneal epithelium was significantly thicker in eyes treated with AST eye drops, compared to those treated with vehicles (p < 0.01), in a doses dependent manner. Significantly fewer apoptotic cells were observed in AST-treated eyes than controls after irradiation (p < 0.01). AST also reduced oxidative stress in irradiated corneas. The in vitro study showed less cytotoxicity of TKE2 cells in AST-treated cultures after UVB-irradiation (p < 0.01). The cytoprotective effect increased with the dose of AST.
Conclusions: Topical AST administration may be a candidate treatment to limit the damages by UV irradiation with wide clinical applications.

Immunolocalization of Vascular Adhesion Protein-1 in Human Conjunctival Tumors
Junichi Fukuhara, Satoru Kase, Kousuke Noda, Miyuki Murata, Mika Noda, Ryo Ando, Zhenyu Dong, Atsuhiro Kanda, Susumu Ishida
OPHTHALMIC RESEARCH, 48, 1, 33, 37, KARGER, 2012年, ［査読有り］
英語, 研究論文（学術雑誌）, 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. Copyright (c) 2012 S. Karger AG, Basel

GEP100-Arf6-AMAP1-Cortactin Pathway Frequently Used in Cancer Invasion Is Activated by VEGFR2 to Promote Angiogenesis
Ari Hashimoto, Shigeru Hashimoto, Ryo Ando, Kosuke Noda, Eiji Ogawa, Hirokazu Kotani, Mayumi Hirose, Toshi Menju, Masaki Morishige, Toshiaki Manabe, Yoshinobu Toda, Susumu Ishida, Hisataka Sabe
PLOS ONE, 6, 8, e23359, PUBLIC LIBRARY SCIENCE, 2011年08月, ［査読有り］
英語, 研究論文（学術雑誌）, Angiogenesis and cancer invasiveness greatly contribute to cancer malignancy. Arf6 and its effector, AMAP1, are frequently overexpressed in breast cancer, and constitute a central pathway to induce the invasion and metastasis. In this pathway, Arf6 is activated by EGFR via GEP100. Arf6 is highly expressed also in human umbilical vein endothelial cells (HUVECs) and is implicated in angiogenesis. Here, we found that HUVECs also highly express AMAP1, and that vascular endothelial growth factor receptor-2 (VEGFR2) recruits GEP100 to activate Arf6. AMAP1 functions by binding to cortactin in cancer invasion and metastasis. We demonstrate that the same GEP100-Arf6-AMAP1-cortactin pathway is essential for angiogenesis activities, including cell migration and tubular formation, as well as for the enhancement of cell permeability and VE-cadherin endocytosis of VEGF-stimulated HUVECs. Components of this pathway are highly expressed in pathologic angiogenesis, and blocking of this pathway effectively inhibits VEGF-or tumor-induced angiogenesis and choroidal neovascularization. The GEP100-Arf6-AMAP1-cortactin pathway, activated by receptor tyrosine kinases, appears to be common in angiogenesis and cancer invasion and metastasis, and provides their new therapeutic targets.

Tissue factor expression in human pterygium
Ryo Ando, Satoru Kase, Tsutomu Ohashi, Zhenyu Dong, Junichi Fukuhara, Atsuhiro Kanda, Miyuki Murata, Kousuke Noda, Nobuyoshi Kitaichi, Susumu Ishida
MOLECULAR VISION, 17, 8-10, 63, 69, MOLECULAR VISION, 2011年01月, ［査読有り］
英語, 研究論文（学術雑誌）, 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. Formalin-fixed, 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 (alpha-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 pterygial epithelial cells was significantly higher than in normal conjunctival epithelial cells (p<0.001). TF immunoreactivity was detected in alpha-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.

Central serous retinal detachment detected by optical coherence tomography in Leber's idiopathic stellate neuroretinitis
R Ando, Y Shinmei, T Nitta, K Yoshida, S Chin, M Kase, S Ohno
JAPANESE JOURNAL OF OPHTHALMOLOGY, 49, 6, 547, 548, ELSEVIER SCIENCE INC, 2005年11月, ［査読有り］
英語

弱視治療をおこなった広汎な網膜有髄神経線維の4例　　　　　　　　　　　　　　　
福津 佳苗, 安藤 亮, 野崎 真世, 溝口 亜矢子, 石田 晋, 眼科臨床紀要, 11, 4, 300, 300, 2018年04月
眼科臨床紀要会, 日本語

眼科のトランスレーショナルリサーチ 多機能蛋白質に着目した糖尿病網膜症に対する創薬研究
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
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), (公財)日本眼科学会, 日本語

抗VEGF治療セミナー VEGF阻害薬の作用機序
安藤 亮, 野田 航介, あたらしい眼科, 35, 1, 105, 106, 2018年01月
現在、わが国で眼科領域において使用されているVEGF阻害薬にはベバシズマブ、ペガプタニブ、ラニビズマブ、アフリベルセプトの4種類がある。実臨床ではそれぞれの特性を理解したうえで選択、使用されるべきである。本稿では各薬剤の特性と作用機序について概説する。(著者抄録), (株)メディカル葵出版, 日本語

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
眼科臨床紀要会, 日本語

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
眼科臨床紀要会, 日本語

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
眼科臨床紀要会, 日本語

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
眼科臨床紀要会, 日本語

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
眼科臨床紀要会, 日本語

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
眼科臨床紀要会, 日本語

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
(公財)日本眼科学会, 日本語

切腱しない筋移動術を行ったDouble Elevator Palsy　　　　　　　　　　　　　　　
白枝 友子, 安藤 亮, 野崎 真世, 新明 康弘, 溝口 亜矢子, 阿部 朋子, 石田 晋, 眼科手術, 30, 1, 174, 177, 2017年01月
背景:外転神経麻痺に対する術式として、切腱を伴わない垂直筋移動術(西田法)が報告されている。今回、筆者らはdouble elevator palsy(DEP)の症例に対して、その術式を水平筋に応用し施行したので報告する。症例:0歳4ヵ月、女児。生下時からの眼位異常の精査目的に北海道大学病院眼科へ紹介となった。初診時、Hirschberg 15°の左下斜視があり、左眼では著明な上転制限と眼瞼下垂を認めた。MRIにて頭蓋内病変は否定され、Bell現象陽性であることから、核上性DEPと診断した。5歳時、35Δの左下斜視に対し、患眼に切腱を伴わない水平筋上方移動術を施行した。術中、外直筋が通常よりも半筋腹下方に付着していたため、移動量は予定よりも少なくなった。術後の斜視角は16Δの左下斜視に改善した。初回手術の6ヵ月後に左下直筋後転術(4mm)を追加し、術後は5Δの左下斜視となった。所見:本症例に対する水平筋上方移動術の手術効果は19Δであった。この結果は西田法本来の眼位矯正効果よりも低矯正であったが、これは外直筋の付着異常により水平筋を十分に上方へ移動できなかったことが一因と考えられた。結論:DEPに対して切腱を伴わない水平筋上方移動術は有効な術式であると考えられた。(著者抄録), (公社)日本眼科手術学会, 日本語

三角症候群の1例における脈絡膜循環動態と形態の経時変化　　　　　　　　　　　　　　　
石川 由梨, 橋本 勇希, 齋藤 航, 安藤 亮, 溝口 亜矢子, 石田 晋, 日本視能訓練士協会誌, 45, 356, 357, 2016年12月
(公社)日本視能訓練士協会, 日本語

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
眼科臨床紀要会, 日本語

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
眼科臨床紀要会, 日本語

2型脈絡膜新生血管を伴った加齢黄斑変性に対するPDTトリプル療法の治療成績　　　　　　　　　　　　　　　
森 祥平, 齋藤 航, 齋藤 理幸, 安藤 亮, 廣岡 季里子, 吉澤 史子, 野田 航介, 石田 晋, 眼科臨床紀要, 9, 11, 932, 933, 2016年11月
眼科臨床紀要会, 日本語

Alterations of Choroidal Thickness and Circulation in Patients with Hypertensive Choroidopathy
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
ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 英語, 研究発表ペーパー・要旨（国際会議）

抗α-enolase抗体が陽性となった黄斑浮腫合併網膜色素変性の1例　　　　　　　　　　　　　　　
橋本 勇希, 齋藤 航, 神田 敦宏, 安藤 亮, 石田 晋, 眼科臨床紀要, 9, 8, 672, 672, 2016年08月
眼科臨床紀要会, 日本語

後天性滑車神経麻痺に対する垂直筋水平移動術の手術効果
石垣 さやか, 新明 康弘, 安藤 亮, 野崎 真世, 溝口 亜矢子, 阿部 朋子, 陳 進輝, 石田 晋, 眼科臨床紀要, 9, 4, 323, 327, 2016年04月
目的:後天性滑車神経麻痺に対して患眼の垂直筋水平移動術を行い、その手術効果について検討した。対象および方法:対象は2003〜2013年までに北海道大学病院眼科を受診し、後天性滑車神経麻痺と診断され患眼の垂直筋水平移動術を行った5例である。回旋斜視と上斜視に対して患眼の下直筋鼻側移動術と短縮術を3例、上直筋耳側移動術と後転術を1例、下直筋鼻側移動術のみを1例に行った。また、垂直筋の短縮または後転術を行った麻痺性斜視患者10例をコントロール群とした。結果:外方回旋斜視に対する垂直筋水平移動術の手術効果は、1筋腹あたり4.7±1.7°であった。上下偏位に対する垂直筋短縮後転術の手術効果は1mmあたり0.4±1.0°であったのに対して、コントロール群における上下偏位に対する手術効果は1mmあたり1.5±1.1°であった(P=0.14)。結論:後天性滑車神経麻痺による外方回旋斜視に対する患眼の垂直筋水平移動術は、有効な術式と考えられた。(著者抄録), 眼科臨床紀要会, 日本語

当科における先天性眼瞼下垂に伴った屈折異常と弱視の検討　　　　　　　　　　　　　　　
野崎 真世, 安藤 亮, 溝口 亜矢子, 石嶋 漢, 野田 実香, 吉田 和彦, 石田 晋, 眼科臨床紀要, 9, 4, 372, 372, 2016年04月
眼科臨床紀要会, 日本語

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
(公財)日本眼科学会, 日本語

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
(公財)日本眼科学会, 日本語

中心性漿液性脈絡網膜症患者に対する寒冷刺激試験後の脈絡膜循環変化　　　　　　　　　　　　　　　
齋藤 理幸, 齋藤 航, 橋本 勇希, 廣岡 季里子, 安藤 亮, 森 祥平, 野田 航介, 石田 晋, 眼科臨床紀要, 8, 11, 825, 826, 2015年11月
眼科臨床紀要会, 日本語

近視性黄斑分離に対する内境界膜剥離併用硝子体手術成績　　　　　　　　　　　　　　　
森 祥平, 齋藤 航, 齋藤 理幸, 安藤 亮, 廣岡 季里子, 野田 航介, 石田 晋, 眼科臨床紀要, 8, 11, 834, 835, 2015年11月
眼科臨床紀要会, 日本語

三角症候群の1例における脈絡膜循環動態と形態の経時変化　　　　　　　　　　　　　　　
石川 由梨, 橋本 勇希, 齋藤 航, 安藤 亮, 溝口 亜矢子, 石田 晋, 日本視能矯正学会プログラム抄録集, 56回, 81, 81, 2015年10月
日本視能矯正学会, 日本語

後天性滑車神経麻痺に対する上下直筋水平移動術の手術効果　　　　　　　　　　　　　　　
石垣 さやか, 新明 康弘, 安藤 亮, 野崎 真世, 溝口 亜矢子, 阿部 朋子, 清水 啓史, 横山 千秋, 陳 進輝, 石田 晋, 眼科臨床紀要, 8, 7, 510, 511, 2015年07月
眼科臨床紀要会, 日本語

【糖尿病網膜症2015年】 糖尿病網膜症・黄斑浮腫の分子病態
安藤 亮, 野田 航介, あたらしい眼科, 32, 3, 327, 330, 2015年03月
(株)メディカル葵出版, 日本語

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
(公財)日本眼科学会, 日本語

急性帯状潜在性網膜外層症における視機能を規定する因子　　　　　　　　　　　　　　　
齋藤 航, 齊藤 沙宝, 齋藤 理幸, 橋本 勇希, 森 祥平, 安藤 亮, 野田 航介, 南場 研一, 石田 晋, 日本眼科学会雑誌, 119, 臨増, 182, 182, 2015年03月
(公財)日本眼科学会, 日本語

特発性黄斑円孔手術前後における網膜内層厚層別解析　　　　　　　　　　　　　　　
橋本 勇希, 齋藤 航, 廣岡 季里子, 森 祥平, 齋藤 理幸, 安藤 亮, 野田 航平, 石田 晋, 日本眼科学会雑誌, 119, 臨増, 233, 233, 2015年03月
(公財)日本眼科学会, 日本語

間歇性外斜視の手術後に過矯正となった症例の検討　　　　　　　　　　　　　　　
阿部 朋子, 安藤 亮, 溝口 亜矢子, 石垣 さやか, 山口 淑子, 野崎 真世, 石田 晋, 日本視能訓練士協会誌, 43, 338, 338, 2014年12月
(公社)日本視能訓練士協会, 日本語

小児における網脈絡膜形態の検討　　　　　　　　　　　　　　　
橋本 勇希, 齋藤 航, 廣岡 季里子, 齋藤 理幸, 安藤 亮, 吉澤 史子, 野田 航介, 石田 晋, 眼科臨床紀要, 7, 5, 386, 387, 2014年05月
眼科臨床紀要会, 日本語

糖尿病網膜症における前房水中PIGF濃度の検討　　　　　　　　　　　　　　　
安藤 亮, 野田 航介, 難波 志帆, 石嶋 漢, 藤谷 顕雄, 吉沢 史子, 新明 康弘, 齋藤 航, 神田 敦宏, 石田 晋, 日本眼科学会雑誌, 118, 臨増, 265, 265, 2014年03月
(公財)日本眼科学会, 日本語

単焦点眼鏡へ移行できた後に眼位変動を来した非屈折性調節性内斜視の長期経過　　　　　　　　　　　　　　　
溝口 亜矢子, 安藤 亮, 山口 淑子, 石垣 さやか, 石田 晋, 日本視能訓練士協会誌, 42, 239, 240, 2013年12月
(公社)日本視能訓練士協会, 日本語

間歇性外斜視の手術後に過矯正となった症例の検討　　　　　　　　　　　　　　　
阿部 朋子, 安藤 亮, 溝口 亜矢子, 石垣 さやか, 山口 淑子, 野崎 真世, 石田 晋, 日本視能矯正学会プログラム抄録集, 54回, 79, 79, 2013年11月
日本視能矯正学会, 日本語

SRPK阻害薬による脈絡膜血管新生の抑制効果　　　　　　　　　　　　　　　
董 震宇, 野田 航介, 斉藤 航, 木下 哲志, 福原 淳一, 安藤 亮, 村田 美幸, 神田 敦宏, 萩原 正敏, 石田 晋, 日本眼科学会雑誌, 117, 臨増, 289, 289, 2013年03月
(公財)日本眼科学会, 日本語

マウス脈絡膜新生血管モデルにおけるゲニステインの抑制効果　　　　　　　　　　　　　　　
木下 哲志, 野田 航介, 高階 沙織, 董 陽子, 福原 淳一, 董 震宇, 安藤 亮, 神田 敦宏, 石田 晋, 日本眼科学会雑誌, 117, 臨増, 289, 289, 2013年03月
(公財)日本眼科学会, 日本語

マウス脈絡膜新生血管モデルにおけるケルセチンの抑制効果　　　　　　　　　　　　　　　
福原 淳一, 野田 航介, 高階 沙織, 董 陽子, 木下 哲志, 董 震宇, 安藤 亮, 神田 敦宏, 石田 晋, 日本眼科学会雑誌, 117, 臨増, 289, 289, 2013年03月
(公財)日本眼科学会, 日本語

プロテアソーム機能不全による網膜変性　　　　　　　　　　　　　　　
安藤 亮, 野田 航介, 外丸 詩野, 野田 実香, 高階 沙織, 董 陽子, 木下 哲志, 福原 淳一, 董 震宇, 神田 敦宏, 石田 晋, 日本眼科学会雑誌, 117, 臨増, 312, 312, 2013年03月
(公財)日本眼科学会, 日本語

ぶどう膜炎における網羅的糖鎖解析　　　　　　　　　　　　　　　
南場 研一, 北市 伸義, 安藤 亮, 竹本 裕子, 水内 一臣, 堀江 幸弘, 大野 重昭, 天野 麻穂, 西村 紳一郎, 石田 晋, 日本眼科学会雑誌, 117, 臨増, 318, 318, 2013年03月
(公財)日本眼科学会, 日本語

増殖糖尿病網膜症における硝子体中可溶型VAP-1とプロレニン　　　　　　　　　　　　　　　
高階 沙織, 野田 航介, 難波 志帆, 木下 哲志, 福原 淳一, 董 震宇, 安藤 亮, 吉澤 史子, 斎藤 航, 神田 敦宏, 石田 晋, 日本眼科学会雑誌, 117, 臨増, 366, 366, 2013年03月
(公財)日本眼科学会, 日本語

単焦点眼鏡へ移行できた後に眼位変動を来した非屈折性調節性内斜視の長期経過　　　　　　　　　　　　　　　
溝口 亜矢子, 安藤 亮, 山口 淑子, 石垣 さやか, 石田 晋, 日本視能矯正学会プログラム抄録集, 53回, 73, 73, 2012年11月
日本視能矯正学会, 日本語

毒性終末糖化産物阻害薬による自己免疫性ぶどう膜網膜炎の軽症化　　　　　　　　　　　　　　　
董 震宇, 北市 伸義, 岩田 大樹, 竹内 正義, 安藤 亮, 福原 淳一, 木下 哲志, 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, 249, 249, 2012年03月
(公財)日本眼科学会, 日本語

マウス脈絡膜新生血管モデルにおけるカリジノゲナーゼの血管新生抑制効果　　　　　　　　　　　　　　　
福原 淳一, 野田 航介, 吉澤 史子, 木下 哲志, 董 震宇, 安藤 亮, アントン・レニコフ, 神田 敦宏, 石田 晋, 日本眼科学会雑誌, 116, 臨増, 256, 256, 2012年03月
(公財)日本眼科学会, 日本語

増殖糖尿病網膜症におけるVEGF阻害剤の硝子体内VAP-1濃度への影響　　　　　　　　　　　　　　　
安藤 亮, 野田 航介, 村田 美幸, 難波 志帆, 木下 哲志, 福原 淳一, 董 震宇, アントン・レニコフ, 齋藤 航, 神田 敦宏, 石田 晋, 日本眼科学会雑誌, 116, 臨増, 265, 265, 2012年03月
(公財)日本眼科学会, 日本語

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
(公財)日本眼科学会, 日本語

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
(公財)日本眼科学会, 日本語

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
(公財)日本眼科学会, 日本語

増殖糖尿病網膜症患者の硝子体液におけるVAP-1濃度　　　　　　　　　　　　　　　
福原 淳一, 野田 航介, 村田 美幸, 齋藤 航, 董 震宇, 安藤 亮, アントン・レニコフ, 神田 敦宏, 石田 晋, 日本眼科学会雑誌, 115, 臨増, 231, 231, 2011年04月
(公財)日本眼科学会, 日本語

ヒト初発翼状片の病理組織学的検討
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。, 札幌社会保険総合病院, 日本語

インドシアニングリーン蛍光眼底造影を行った網膜海綿状血管腫の1例　　　　　　　　　　　　　　　
安藤 亮, 齋藤 航, 横井 匡彦, 古館 直樹, 大野 重昭, 眼科臨床医報, 99, 9, 747, 749, 2005年09月
12歳男児.学校における視力検査により精査を勧められた.初診時の両眼矯正視力1.0であった.右眼底では,下方の赤道部網膜に,暗褐色で球状腫瘤から成るぶどう房状の腫瘍を認め,白色の膜状物を伴っていた.また,フルオレセイン蛍光眼底造影(FA),走査レーザー検眼鏡を用いたインドシアニングリーン蛍光眼底造影(IA)では,周囲の球状腫瘤から造影され徐々に腫瘤中央への流入を認め,血漿血球分離を明瞭に認めた.以上の所見より,網膜海綿状血管腫(本疾患)と診断し,経過観察とした.日本における本疾患の報告は今までに20数例のみで,IAを行った報告は殆どない, 眼科臨床医報会, 日本語

網脈絡膜組織に対する網膜色素上皮由来胎盤成長因子の保護効果
科学研究費助成事業
2018年04月01日 - 2021年03月31日
安藤 亮
胎盤成長因子(PlGF)は血管新生や血管形成に関与する血管内皮増殖因子(VEGF)ファミリーの一員である。近年、VEGFファミリー分子の持つ組織保護作用について認識が深まりつつあるが、PlGFの生理的作用は不明であった。本研究では、網膜の恒常性維持に重要な働きをする網膜色素上皮細胞（RPE）に対するPlGFの生理的役割を解析し、PlGFが蛋白の分解系への輸送に重要な分子GSK-3の活性を抑制することでVEGF受容体（VEGFR）-2蛋白を安定化し、VEGF/VEGFR-2によるRPE細胞保護作用を支える働きを有することを明らかにした。
日本学術振興会, 若手研究, 北海道大学, 18K16915

結膜EMZLにおけるRAS系の関与
科学研究費助成事業
2015年04月01日 - 2018年03月31日
安藤 亮
組織レニン・アンジオテンシン系（組織renin-angiotensin system: RAS）および受容体結合プロレニン系（receptor-associated prorenin system: RAPS）は、糖尿病網膜症をはじめとする様々な眼疾患において血管新生などの病態に関与することを、我々はこれまでに報告してきた。本研究では、結膜節外辺縁帯B細胞性リンパ腫（EMZL）におけるRASおよびRAPSの病態への関与を検討した。その結果、組織RASおよびRAPSが結膜EMZLの病態形成に関与する分子であることが示唆された。
日本学術振興会, 若手研究(B), 北海道大学, 15K20241