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福津　佳苗 (フクツ　カナエ)

医学研究院助教

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研究活動情報

■ 受賞
  • 2025年03月, Fuji Retina, Best Poster Award 1st place
    福津 佳苗
  • 2024年01月, 37th Singapore-Malaysia Joint Meeting, Best free paper presentation (2nd prize)
    Arteriosclerosis and Retinal Vascular Area with Axial Length Correction
    福津 佳苗
  • 2023年03月, 日本微小循環学会, 第48回日本微小循環学会 学会奨励賞 優秀賞
    Establishment of deep learning algorithm for retinal vascular area measurement: an alternative biomarker of brachial-ankle pulse wave velocity
    福津 佳苗
  • 2023年03月, 北海道大学, 北海道大学大塚賞
    福津 佳苗
  • 2022年09月, 北海道大学大学院医学研究院, 第18回音羽博次奨学基金奨学金
    福津 佳苗
  • 2021年01月, All English Web Seminar, Gold Award
    Role of Acrolein and ROCK1 in retinal glial cells
    福津 佳苗
  • 2014年11月, Tokyo Retina League, Young Investigator Award
    福津 佳苗
■ 論文
  • Advancing perspectives on proliferative vitreoretinopathy: Updates in experimental research and emerging clinical treatments
    Fang Zheng; Elie Motulsky; Luiz Roisman; Xiaoyun Fang; Kanae Fukutsu; Chee Wai Wong; Veluchamy Amutha Barathi; Edmund Wong; Andrew S.H. Tsai; Leo A. Kim; Gavin SW Tan
    Asia-Pacific Journal of Ophthalmology, 15, 2, 100302, 100302, Elsevier BV, 2026年03月
    研究論文（学術雑誌）
  • Oculomics and AI: The eye as a biomarker for health span
    Joy Le Yi Wong; Haoran Cheng; Wen Jun Peh; Dean Ho; Tien Y. Wong; Celene Yan Yan Hui; Darren S.J. Ting; Yong Mong Bee; Su Yen Goh; Rajendra S. Apte; Vinit B. Mahajan; Jeffrey L. Goldberg; Evelyne Bischof; David A. Sinclair; Carol C. Cheung; Hiok Hong Chan; Kanae Fukutsu; Ting Fang Tan; Chrystie Wan Ning Quek; Ashley Shuen Ying Hong; Li Yuan Jin; Siegfried Karl Wagner; Pearse Keane; Daniela Ferrara; Malvina Eydelman; Dennis S.C. Lam; Xiaomeng Wang; Daniel S.W. Ting
    Asia-Pacific Journal of Ophthalmology, 15, 1, 100282, 100282, Elsevier BV, 2026年01月
    研究論文（学術雑誌）
  • Acrolein Promotes Retinal Inflammation Through Macrophage Chemotaxis by Inducing CCL2 Production From Müller Cells
    Kanae Fukutsu; Miyuki Murata; Kasumi Kikuchi; Kousuke Noda; Susumu Ishida
    The FASEB Journal, 40, 1, Wiley, 2025年12月30日
    研究論文（学術雑誌）, ABSTRACT

    This study aimed to investigate the inflammatory mechanisms induced by the toxic aldehyde acrolein in proliferative diabetic retinopathy (PDR). N ε ‐(3‐formyl‐3, 4‐dehydropiperidino) lysine adduct (FDP‐lys), an acrolein‐binding protein, and chemokine (C‐C motif) ligand‐2 (CCL2) levels in human vitreous fluid obtained from patients with PDR were measured using Luminex assay and ELISA. A rat Müller glial cell line (TR‐MUL5) was exposed to acrolein (10–50 μM), and CCL2 expression was evaluated using real‐time PCR and ELISA. Macrophage (RAW264.7) migration under the presence of acrolein‐stimulated TR‐MUL5 was assessed using a Transwell assay. High mobility group box‐1 (HMGB1) translocation in TR‐MUL5 was examined by immunofluorescence and cell fractionation. These analyses demonstrated that FDP‐lys and CCL2 concentrations in the vitreous of patients with PDR were markedly higher than those in controls ( n  = 12, p  < 0.01), and a significant correlation was observed between the two ( R  = 0.60, p  < 0.05). Acrolein stimulation upregulated Ccl2 expression in TR‐MUL5 cells (3.5 ± 0.4‐fold at 25 μM; 10 ± 1.4‐fold at 50 μM, n  = 3, p  < 0.01) and increased CCL2 protein levels dose‐dependently ( n  = 3, p  < 0.01). Macrophage migration increased 2.2 ± 0.3‐fold with acrolein‐stimulated TR‐MUL5 but was attenuated by the CCR2 inhibitor RS504393 ( n  = 3, p  < 0.01). Acrolein‐induced HMGB1 translocation was confirmed in TR‐MUL5, and glycyrrhizin, an HMGB1 inhibitor, reduced CCL2 levels. In conclusion, acrolein promotes PDR progression by enhancing macrophage migration through CCL2 secretion and HMGB1 translocation in Müller cells.
  • Artificial intelligence oculomics for systemic health and longevity medicine: 2025 and beyond
    Jie Yao; Ashley Shuen Ying Hong; Kanae Fukutsu; Daniel Shu Wei Ting
    Current Opinion in Ophthalmology, 36, 6, 477, 486, Ovid Technologies (Wolters Kluwer Health), 2025年09月03日
    研究論文（学術雑誌）, Purpose of review

    With the rise of ‘oculomics’ and the application of advanced artificial intelligence techniques in healthy ageing, retinal imaging, the only way we can directly visualize the microvascular circulation, is expanding beyond ophthalmology into broader systemic health monitoring. The purpose of this review is to summarize recent advances in this rapidly evolving field and assess the opportunities, challenges, and future directions of the use of oculomics in translating into real-world clinical use.

    Recent findings

    Retinal imaging modalities, such as color fundus photography, optical coherence tomography (OCT), OCT angiography (OCTA), and wide-field imaging, are increasingly integrated with deep learning algorithms to detect, predict, and manage a broad spectrum of systemic diseases, including cardiovascular, cerebrovascular, renal, metabolic, and neurodegenerative disorders, as well as less commonly studied conditions. While research in more established areas is beginning to address clinical translation and implementation, significant challenges remain before these technologies can be reliably adopted in long-term, real-world healthcare settings.

    Summary

    Artificial intelligence applied to retinal imaging has matured from proof-of-concept classifiers to externally validated, occasionally regulated tools that noninvasively profile systemic conditions. Multiplexed foundation models and multimodal transformers herald a shift toward holistic ‘oculomics’ platforms, yet prospective multicenter trials, equitable performance auditing, and health-economic evaluations are essential before widescale clinical adoption.
  • Retinal Arteriovenous Information Improves the Prediction Accuracy of Deep Learning-Based baPWV Index From Color Fundus Photographs.
    Michiyuki Saito; Mizuho Mitamura; Kanae Fukutsu; Dong Zhenyu; Ryo Ando; Satoru Kase; Satoshi Katsuta; Susumu Ishida
    Investigative ophthalmology & visual science, 66, 2, 63, 63, 2025年02月03日, ［国際誌］
    英語, 研究論文（学術雑誌）, PURPOSE: To compare the prediction accuracy of brachial-ankle pulse wave velocity (baPWV) from color fundus photographs (CFPs) using different deep learning models. METHODS: This retrospective study analyzed the data of 696 participants whose baPWVs and CFPs were obtained during medical checkups. Arteriolar and venular probability maps, which were automatically calculated from the CFPs based on our modified deep U-net, Hokkaido University retinal vessel segmentation (HURVS) model, were applied as channel attention to retinal vessel location information to predict baPWV. The baPWV prediction parameters consisted of predicted baPWVs from a single-input model using CFPs only and from a three-input model using CFPs, and arteriolar and venular probability maps. The single- and three-input models adopted a common depth-wise net and were separately pretrained and trained with fivefold cross-validation. These baPWV prediction parameters were corrected using multiple regression equations with age, sex, and systolic blood pressure and were defined as single- and three-input regression-predicted baPWVs. The main outcome measures were the correlation coefficients between true baPWV and the baPWV prediction parameters. RESULTS: The correlation coefficient with true baPWVs was higher for the three-input predicted baPWVs (R = 0.538) than for the single-input predicted baPWVs (R = 0.527). After regression, the three-input, regression-predicted baPWVs (R = 0.704) had the highest prediction accuracy, followed by the single-input, regression-predicted baPWVs (R = 0.692). CONCLUSIONS: The three-input model predicted true baPWVs with high accuracy. This improved prediction accuracy by channel attention to the arteriolar and venular probability maps based on the HURVS model confirmed that arterioles and venules are relevant regions for baPWV prediction.
  • Sex Differences in Age-Related Changes in Retinal Arteriovenous Area Based on Deep Learning Segmentation Model.
    Mizuho Mitamura; Michiyuki Saito; Kanae Fukutsu; Zhenyu Dong; Ryo Ando; Satoru Kase; Kousuke Noda; Ryosuke Shiba; Naoki Isogai; Mitsuru Dohke; Manabu Kase; Susumu Ishida
    Ophthalmology science, 5, 3, 100719, 100719, 2025年, ［国際誌］
    英語, 研究論文（学術雑誌）
  • Relationship between Brachial-Ankle Pulse Wave Velocity and Fundus Arteriolar Area Calculated Using a Deep-Learning Algorithm.
    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, ［国際誌］
    英語, 研究論文（学術雑誌）, 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.
  • The Expression of Matrix Metalloproteinases in Eyes with Intraocular Lymphoma.
    Kanae Fukutsu; Satoru Kase; Daiju Iwata; Kayo Suzuki; Kenichi Namba; Susumu Ishida
    Ocular immunology and inflammation, 30, 7-8, 1798, 1802, 2022年, ［国際誌］
    英語, 研究論文（学術雑誌）, PURPOSE: The purpose of this study is to investigate matrix metalloproteinases (MMPs) expression in human intraocular lymphoma (IOL). METHODS: Two enucleated eyes and seven cell-block samples obtained from patients with IOL who underwent vitrectomy were used. Immunopathological examinations were performed for detection of MMP-2, MMP-9, and TIMP-4 expressions. RESULTS: In the enucleated eye with primary IOL (PIOL), MMP-2 was negative, and MMP-9 and TIMP-4 were positive in the lymphoma cells, while in the enucleated eye with secondary IOL (SIOL), all the molecules were positive. Among the cell-block samples with PIOL, the positive rate in lymphoma cells of MMP-2, MMP-9, and TIMP-4 was 75%, 100%, and 75%, respectively. In the cell-block samples with SIOL, the positive rates of MMP-2, MMP-9, and TIMP-4 were all 100%. CONCLUSIONS: MMP-2, MMP-9, and TIMP-4 were expressed in lymphoma cells using the specimens of human IOL, suggesting that MMPs may play an important role in the development of IOL.
  • A Deep Learning Architecture for Vascular Area Measurement in Fundus Images.
    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, 1, 1, 100004, 100004, 2021年03月, ［国際誌］
    英語, 研究論文（学術雑誌）, PURPOSE: To develop a novel evaluation system for retinal vessel alterations caused by hypertension using a deep learning algorithm. DESIGN: Retrospective study. PARTICIPANTS: Fundus photographs (n = 10 571) of health-check participants (n = 5598). METHODS: The participants were analyzed using a fully automatic architecture assisted by a deep learning system, and the total area of retinal arterioles and venules was assessed separately. The retinal vessels were extracted automatically from each photograph and categorized as arterioles or venules. Subsequently, the total arteriolar area (AA) and total venular area (VA) were measured. The correlations among AA, VA, age, systolic blood pressure (SBP), and diastolic blood pressure were analyzed. Six ophthalmologists manually evaluated the arteriovenous ratio (AVR) in fundus images (n = 102), and the correlation between the SBP and AVR was evaluated manually. MAIN OUTCOME MEASURES: Total arteriolar area and VA. RESULTS: The deep learning algorithm demonstrated favorable properties of vessel segmentation and arteriovenous classification, comparable with pre-existing techniques. Using the algorithm, a significant positive correlation was found between AA and VA. Both AA and VA demonstrated negative correlations with age and blood pressure. Furthermore, the SBP showed a higher negative correlation with AA measured by the algorithm than with AVR. CONCLUSIONS: The current data demonstrated that the retinal vascular area measured with the deep learning system could be a novel index of hypertension-related vascular changes.
  • ROCK1 Mediates Retinal Glial Cell Migration Promoted by Acrolein.
    Kanae Fukutsu; Miyuki Murata; Kasumi Kikuchi; Shiho Yoshida; Kousuke Noda; Susumu Ishida
    Frontiers in medicine, 8, 717602, 717602, 2021年, ［国際誌］
    英語, 研究論文（学術雑誌）, Objective: Acrolein is a highly reactive aldehyde that covalently binds to cellular macromolecules and subsequently modulates cellular function. Our previous study demonstrated that acrolein induces glial cell migration, a pathological hallmark of diabetic retinopathy; however, the detailed cellular mechanism remains unclear. The purpose of this study was to investigate the role of acrolein in retinal glial cell migration by focusing on rho-associated coiled-coil-containing protein kinases (ROCKs). Methods: Immunofluorescence staining for ROCK isoforms was performed using sections of fibrovascular tissue obtained from the eyes of patients with proliferative diabetic retinopathy (PDR). Rat retinal Müller glial cell line, TR-MUL5, was stimulated with acrolein and the levels of ROCK1 were evaluated using real-time PCR and western blotting. Phosphorylation of the myosin-binding subunit of myosin light chain phosphatase [myosin phosphatase target subunit 1, (MYPT1)] and myosin light chain 2 (MLC2) was assessed. The cell migration rate of TR-MUL5 cells exposed to acrolein and/or ripasudil, a non-selective ROCK inhibitor, was measured using the Oris cell migration assay. Results: ROCK isoforms, ROCK1 and ROCK2, were positively stained in the cytosol of glial cells in fibrovascular tissues. In TR-MUL5 cells, the mRNA expression level of Rock1, but not Rock2, was increased following acrolein stimulation. In line with the PCR data, western blotting showed increase in ROCK1 and cleaved ROCK1 protein in TR-MUL5 cells stimulated with acrolein. N-acetylcysteine (NAC) suppressed acrolein-associated Rock1 upregulation in TR-MUL5 cells. Acrolein augmented the phosphorylation of MYPT1 and MLC2 and increased the cell migration rate of TR-MUL5 cells, both of which were abrogated by ripasudil. Conclusions: Our study demonstrated that ROCK1 mediates the migration of retinal glial cells promoted by the unsaturated aldehyde acrolein.
  • 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と単球走化性因子
    村田 美幸; 福津 佳苗; 野田 航介; 吉田 志帆; 神田 敦宏; 石田 晋
    糖尿病合併症, 34, Suppl.1, 262, 262, (一社)日本糖尿病合併症学会, 2020年11月
    日本語
  • Pseudo-inflammatory manifestations of choroidal lymphoma resembling Vogt-Koyanagi-Harada disease: case report based on multimodal imaging.
    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, ［国際誌］
    英語, 研究論文（学術雑誌）, 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.
  • The clinical features of radiation cataract in patients with ocular adnexal mucosa-associated lymphoid tissue lymphoma.
    Kanae Fukutsu; Satoru Kase; Kan Ishijima; Rumiko Kinoshita; Susumu Ishida
    Radiation oncology (London, England), 13, 1, 95, 95, 2018年05月16日, ［国際誌］
    英語, 研究論文（学術雑誌）, 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.
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