Faculty Profiles - ARIMA MITSURU

Information

写真a

ARIMA MITSURU

Organization

Kyushu University Hospital Center for Clinical and Translational Research Information Counter Lecturer
School of Medicine Department of Medicine（Concurrent）

Tel

0926424802

Profile

My areas of expertise are translational research, nonclinical development strategy, and regulatory science. In the development of pharmaceuticals, medical devices, and in vitro diagnostics, I focus on the evaluation of nonclinical study results, the assessment of their applicability to humans, and the identification of safety considerations in early-stage development, with the aim of developing strategies that support the practical implementation of research outcomes. At the Pharmaceuticals and Medical Devices Agency (PMDA), I was involved in the clinical evaluation of new drugs, the preparation of review reports, and the assessment of package inserts and risk management plans. I currently work in the Division of Nonclinical Collaboration and Promotion at the Center for Clinical and Translational Research, Kyushu University Hospital, where I support academic research seeds and startups by helping to clarify key issues and develop strategies that connect nonclinical evaluation with regulatory consultation and early clinical development.

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Research Areas

Life Science / Medical technology assessment

Degree

Doctor of Medicine

Research History

Kyushu University 九州大学病院ARO次世代医療センター Lecturer

2026.1 - Present
Kyushu University 九州大学病院ARO次世代医療センター Specially Appointed Lecturer

2020.10 - 2023.9
Kyushu University 九州大学病院 Assistant Professor

2017.4 - 2020.9

Education

Kyushu University 大学院医学研究院

2011.4 - 2015.3

Research Interests・Research Keywords

Research theme： Development of drugs and medical devices

Keyword：規制科学、薬事、非臨床試験、早期臨床開発

Research period： 2026.1 - Present

Awards

学術奨励賞

2020.11 日本糖尿病眼学会
日本眼科学会学術奨励賞

2019.4 日本眼科学会代表的な小児失明原因疾患である未熟児網膜症の重症化を予測する新規因子を同定した。

Papers

Perspective of the Pharmaceuticals and Medical Devices Agency on Drug Development for Childhood Myopia. Reviewed International journal

Mitsuru Arima, Motomasa Atsumi, Kumiko Takeuchi, Takumi Aoki, Emi Inagaki, Yosuke Kobayashi, Takuya Kageyama, Kazuki Izumi, Atsushi Yoshimura, Wataru Asakura

Clinical pharmacology and therapeutics 119 ( 1 ) 26 - 29 2026.1

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Pathologic myopia represents a global public health concern, with increasing prevalence and vision loss risk. Myopia typically develops in childhood and progresses more rapidly with earlier onset. Clinical trials exploring treatments for decelerating myopia progression are underway. In Japan, 0.025% atropine ophthalmic solution (RYJUSEA®) has been approved. This review outlines the evaluation process by the Pharmaceuticals and Medical Devices Agency (PMDA) and highlights challenges for future drug development.

DOI： 10.1002/cpt.70086

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Safety and efficacy of ripasudil eye drops in preterm infants with retinopathy of prematurity: phase 1/2, open label, single-arm trial. Reviewed International journal

Mitsuru Arima, Hirosuke Inoue, Akiko Misumi, Shoko Tsukamoto, Itsuka Matsushita, Shunsuke Araki, Manami Ohta, Kazumasa Takahashi, Miyuki Imazato, Tomoko Goto, Yoshinori Aoki, Koshiro Tagawa, Masayuki Hirose, Yuito Fujita, Noriko Yoshida, Shintaro Nakao, Hiroyuki Kondo, Koichi Kusuhara, Kazuhiro Kimura, Shunji Hasegawa, Yasuhiro Ikeda, Yuki Kodama, Hiroshi Moritake, Masayuki Ochiai, Shouichi Ohga, Junji Kishimoto, Koji Todaka, Ichiro Ieiri, Koh-Hei Sonoda

Japanese journal of ophthalmology 68 ( 5 ) 490 - 499 2024.9 （ ISSN:0021-5155 eISSN:1613-2246 ）

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Authorship：Lead author,　Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Japanese Journal of Ophthalmology

PURPOSE: To assess the safety and efficacy of ripasudil for retinopathy of prematurity (ROP). STUDY DESIGN: Phase 1/2, multicenter, open-label, single-arm, 12-week clinical trial. METHODS: Infants born with gestational age (GA) of ≤ 32 weeks or weight of ≤ 1500 g with zone I or II, ≥ stage 1, ROP in both eyes were enrolled. Ripasudil eye drops were administered to patients in both eyes. Phase 1 was a dose-escalation study (once daily for 1 week, then twice daily for 2 weeks); an additional dosing up to 9 weeks was allowed if no safety issues occurred. In phase 2, ripasudil was administered twice daily for up to 12 weeks. Adverse events were assessed. The proportion of patients with type 1 ROP progression, number of days for type 1 ROP progression, and progression to the most advanced ROP stage were estimated. RESULTS: Twenty-four infants were enrolled (phase 1, n = 3; phase 2, n = 21). Nineteen and four patients experienced systemic and ocular adverse events, respectively. Efficacy endpoints were not different between the ripasudil and historical control groups. However, in the GA ≤ 27 weeks subgroup, fewer patients progressed to type 1 ROP in the ripasudil than in the historical control group (P = 0.09). In the GA ≤ 27 weeks subgroups, the 25th percentile for the number of days for type 1 ROP progression was 22 days in the historical control group and 44 days in the ripasudil group. CONCLUSION: Ripasudil was safe and inhibited/delayed type 1 ROP progression, especially in infants with short GA.

DOI： 10.1007/s10384-024-01100-3

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Claudin-5 Redistribution Induced by Inflammation Leads to Anti-VEGF Resistant Diabetic Macular Edema Reviewed International journal

@Mitsuru Arima,@Shintaro Nakao,@Muneo Yamaguchi,@Hao Feng,@Yuya Fujii,@Kensuke Shibata,@Iori Wada,@Yoshihiro Kaizu,@Hamid Ahmadieh,@Alan W Stitt,@Tatsuro Ishibashi,@Koh-Hei Sonoda

Diabetes 69 ( 5 ) 981 - 989 2020.5

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Neurodevelopmental outcomes following intravitreal bevacizumab injection in Japanese preterm infants with type 1 retinopathy of prematurity Reviewed International journal

@Mitsuru Arima,@Masato Akiyama,@Kohta Fujiwara,@Yujiro Mori,@Hirosuke Inoue,@Eiko Seki,@Takahito Nakama,@Shoko Tsukamoto,@Masayuki Ochiai,@Shouichi Ohga,@Koh-Hei Sonoda

PLoS One 15 ( 3 ) e0230678 2020.3

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Late-onset Circulatory Collapse and Continuous Positive Airway Pressure are Useful Predictors of Treatment-requiring Retinopathy of Prematurity: A 9-year Retrospective Analysis. Reviewed International journal

@Arima M, @Tsukamoto S, Fujiwara K, Murayama M, Fujikawa K, @Sonoda KH.

Sci Rep. 2017.6

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Visual loss caused by retinopathy of prematurity (ROP) will be prevented if treatment-requiring ROP (TR-ROP) can be predicted. In this retrospective study including 418 infants with ≤32 weeks of gestational age (GA) and/or ≤1500 grams of birthweight, we attempted to identify useful predictors. We also examined the efficiency of significant predictors compared with existing predictive models, ROPScore and CHOP model. Multivariable logistic regression analyses supported the following factors were useful for predicting TR-ROP from all infants and infants with any ROP: GA (odds ratio [OR], 0.47 and 0.48), history of late-onset circulatory collapse (LCC) (OR, 2.76 and 2.44) and use of continuous positive airway pressure (CPAP) at 35 weeks of postmenstrual age (OR, 3.78 and 4.50). The comparison of areas under receiver operating characteristic curves indicated the combination of LCC, CPAP and ROPScore was better than ROPScore to predict TR-ROP from all infants and infants with any ROP (P = 0.007 and 0.02) and the combination of LCC, CPAP and CHOP model was also better than CHOP model to predict TR-ROP from all infants and infants with any ROP (P = 0.01 and 0.02). Our results suggested infants with a history of LCC and a long CPAP support have a high incidence of TR-ROP.
Rho-Kinase/ROCK as a Potential Drug Target for Vitreoretinal Diseases. Invited Reviewed International journal

Yamaguchi M, @Nakao S, @Arima M, Wada I, Kaizu Y, Hao F, Yoshida S, @Sonoda KH.

J Ophthalmol. 2017.5

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Basigin can be a therapeutic target to restore the retinal vascular barrier function in the mouse model of diabetic retinopathy. Invited Reviewed International journal

@Arima M, Cui D, Kimura T, @Sonoda KH, @Ishibashi T, Matsuda S, Ikeda E.

Sci Rep. 2016.12

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Vascular Normalization by ROCK Inhibitor: Therapeutic Potential of Ripasudil (K-115) Eye Drop in Retinal Angiogenesis and Hypoxia. Invited Reviewed International journal

Yamaguchi M, @Nakao S, Arita R, Kaizu Y, @Arima M, Zhou Y, Kita T, Yoshida S, Kimura K, Isobe T, Kaneko Y, @Sonoda KH, @Ishibashi T.

Invest Ophthalmol Vis Sci. 2016.4

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ADAM12 and ADAM17 are essential molecules for hypoxia-induced impairment of neural vascular barrier function. Invited Reviewed International journal

Cui D, @Arima M, Takubo K, Kimura T, Horiuchi K, Minagawa T, Matsuda S, Ikeda E.

Sci Rep. 2015.8

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Involvement of periostin in regression of hyaloidvascular system during ocular development. Invited Reviewed International journal

@Arima M, Yoshida S, Nakama T, @Ishikawa K, @Nakao S, Yoshimura T, Asato R, Sassa Y, Kita T, Enaida H, Oshima Y, Matsuda A, Kudo A, @Ishibashi T.

Invest Ophthalmol Vis Sci. 2012.9

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Intravitreal anti-VEGF therapy blocks inflammatory cell infiltration and re-entry into the circulation in retinal angiogenesis. Invited Reviewed International journal

@Nakao S, @Arima M, @Ishikawa K, Kohno R, Kawahara S, Miyazaki M, Yoshida S, Enaida H, Hafezi-Moghadam A, Kono T, @Ishibashi T.

Invest Ophthalmol Vis Sci. 2012.6

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RPE With ROCK-Mediated Epithelial-Mesenchymal Transition as a Key Contributor of Subretinal Fibrosis in AMD. Reviewed International coauthorship International journal

Iori Wada, Keijiro Ishikawa, Muneo Yamaguchi, Shotaro Shimokawa, Ji Rui, Kenichiro Mori, Yoshihiro Kaizu, Mitsuru Arima, Shoji Notomi, Yusuke Murakami, Shigenori Inagaki, Yuta Kohro, Makoto Tsuda, Kensuke Shibata, Ryo Terao, Takeshi Terabayashi, Toshimasa Ishizaki, Shigeo Yoshida, Tatsuro Ishibashi, Susumu Ishida, Rajendra S Apte, Koh-Hei Sonoda, Shintaro Nakao

Investigative ophthalmology & visual science 67 ( 5 ) 33 - 33 2026.5 （ ISSN:0146-0404 eISSN:1552-5783 ）

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Language：English Publishing type：Research paper (scientific journal) Publisher：Investigative Ophthalmology and Visual Science

PURPOSE: To investigate the cellular origin and molecular mechanisms underlying subretinal fibrosis (SRF) in neovascular AMD (nAMD), with a focus on the role of RPE and Rho-associated coiled-coil-containing protein kinase (ROCK)-mediated epithelial-mesenchymal transition (EMT). METHODS: Fate-mapping with lineage tracing, laser capture microdissection, microarray and RT-PCR analyses, immunohistochemistry, and functional assays with ROCK inhibitors (Ripasudil, Belumosudil) were used to assess EMT/endothelial-to-mesenchymal transition contributions to SRF and ROCK pathway involvement. RESULTS: Fate mapping identified RPE and endothelial cells as sources of myofibroblasts. EMT-related gene upregulation and ROCK1/2 expression were observed in SRF lesions. RPE-specific ROCK2 knockout significantly reduced fibrosis and EMT markers. Ripasudil suppressed SRF development and reversed EMT both in vivo and in vitro. ROCK expression was confirmed in human choroidal neovascularization membranes. CONCLUSIONS: RPE-derived myofibroblasts via ROCK2-mediated EMT play a dominant role in SRF formation. ROCK inhibitors, particularly Ripasudil, may serve as effective therapeutic agents against fibrosis in nAMD.

DOI： 10.1167/iovs.67.5.33

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Preclinical Evaluation of Pitavastatin Nanoparticles for Preserving Cone Photoreceptors in Mouse Models of RP. Reviewed International journal

Sakurako Shimokawa, Masatoshi Fukushima, Shotaro Shimokawa, Takahiro Hisai, Yan Tao, Huanyu Zhao, Jun Funatsu, Shoji Notomi, Keijiro Ishikawa, Mitsuru Arima, Chie Kikutake, Mikita Suyama, Kaori Tanaka, Yasuyuki Ohkawa, Koh-Hei Sonoda, Yusuke Murakami

Investigative ophthalmology & visual science 66 ( 13 ) 15 - 15 2025.10 （ ISSN:0146-0404 eISSN:1552-5783 ）

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PURPOSE: We previously demonstrated that intravenous pitavastatin Poly (lactic-co-glycolic acid) nanoparticles (PVS-NPs) reduced monocyte/macrophage activation and mitigated cone-cell death in a mouse model of RP. Here, we sought to optimize the PVS-NP administration regimen and investigated underlying molecular mechanisms by single-cell analyses. METHODS: In our previous study, twice-weekly administration of 0.3 mg/kg PVS-NPs reduced cone-cell degeneration in rd10 mice with Pde6b mutations. Here, we conducted a dose escalation study with weekly injections of 0.1, 0.3, and 1.0 mg/kg PVS-NPs in rd10 mice, followed by interval optimization with monthly and twice-monthly regimens from postnatal day 21 (P21) to P49. The cone-cell density (primary outcome) and photopic b-wave amplitude (secondary outcome) were assessed at P50. Finally, PVS-NP efficacy was validated in RhoP23H mice with Rhodopsin mutations. RESULTS: Cone densities and photopic b-wave amplitudes were approximately doubled in rd10 mice treated weekly with 0.3 or 1.0 mg/kg PVS-NPs compared with PBS-treated controls. Based on the efficacy of a 1.5 mg/kg cumulative dose in the weekly 0.3 mg/kg group, we evaluated lower dose, reduced frequency regimens: twice monthly 0.5 mg/kg (1.0 mg total) and monthly 0.75 mg/kg (0.75 mg total). The monthly 0.75 mg/kg regimen significantly preserved cone-cell density and function in rd10 mice and RhoP23H mice. Single-cell analyses of rd10 retinas and peripheral blood revealed that PVS-NPs shifted monocytes from a proinflammatory to an anti-inflammatory state and reduced their infiltration into the retina. CONCLUSIONS: Monthly intravenous administration of PVS-NPs may be an effective treatment regimen to delay cone-cell degeneration in RP. The therapeutic effect of PVS-NPs likely involves the modulation of circulating inflammatory monocytes and their engraftment.

DOI： 10.1167/iovs.66.13.15

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Intravenous Sodium Iodate Administration Induces Macula-Specific RPE Damage and Rod-Dominant Apoptosis in the Cynomolgus Monkey. Reviewed International journal

Shoji Notomi, Guannan Wu, Takaharu Nagaoka, Nao Yotsumoto, Tomoaki Araki, Mitsuru Arima, Toshio Hisatomi, Koh-Hei Sonoda, Kazutoshi Sawada

Investigative ophthalmology & visual science 66 ( 9 ) 18 - 18 2025.7 （ ISSN:0146-0404 eISSN:1552-5783 ）

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PURPOSE: Although sodium-iodate (SI)-induced retinal degeneration has been extensively studied in rodent models, its macular pathology and cone/rod vulnerability difference remains elusive. This study aims to characterize SI-induced macular pathology in cynomolgus monkeys. METHODS: Intravenous injections of SI were performed on four male cynomolgus monkeys including three young adults (Animal No. 1-3; five to six years old) and one juvenile (Animal No. 4; two years old) from a breeding colony. To optimize dosing, Animal No. 1 received 25 and 37.5 mg/kg SI; Animal No. 2 received a single SI dose (30 mg/kg) to confirm reproducibility. Animal No. 3 was used to examine subclinical effects at a lower dose (25 mg/kg). Animal No. 4 received increasing doses (30, 35, and 40 mg/kg). Retinal changes were evaluated using fundus photography, fluorescein angiography (FA), and optical coherence tomography (OCT). Histological analysis and transmission electron microscopy (TEM) were also performed. RESULTS: In Animal No. 1, prominent fluorescein leakage by FA and RPE elevation on OCT was observed in the macula after 37.5 mg/kg SI. Histology and TEM revealed that elevated RPE lesion was accompanied by significant RPE migration. Animal No. 2 exhibited similar retinal degeneration. Animal No. 3 exhibited no RPE barrier disruption but showed outer segment damage and RPE melanolipofuscin accumulation. Animal No. 4 showed minimal macular degeneration despite escalating doses. In the peripheral retina, rod apoptosis was evident, whereas macular cone cell death was limited even at high doses. CONCLUSION: Systemic SI administration can induce macular degeneration with RPE barrier disruption in young-adult monkeys, supporting a macula- and cell-type-specific vulnerability.

DOI： 10.1167/iovs.66.9.18

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網膜色素変性症における炎症性マーカーと疾患増悪との関係を評価する前向き自然歴レジストリの研究プロトコル　RP-PRIMARY研究(Study protocol for a prospective natural history registry investigating the relationships between inflammatory markers and disease progression in retinitis pigmentosa: the RP-PRIMARY study) Reviewed International journal

Murakami Yusuke, Hisai Takahiro, Shimokawa Sakurako, Fukushima Masatoshi, Fujiwara Kohta, Hirata Akie, Takada Atsushi, Miyahara Fuyuka, Nakashima Naoki, Kobayakawa Yuko, Arima Mitsuru, Mawatari Go, Ishizu Masataka, Kaida Tomoko, Miyata Kazunori, Ikeda Yasuhiro, Sonoda Koh-Hei

Japanese Journal of Ophthalmology 69 ( 3 ) 378 - 386 2025.5 （ ISSN:0021-5155 ）

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Language：English Publishing type：Research paper (scientific journal) Publisher：シュプリンガー・ジャパン(株)

網膜色素変性症(RP)患者にみられる炎症性マーカーと疾患増悪との関係を評価する前向き自然歴レジストリ(RP-PRIMARY)の研究プロトコルを紹介した。本レジストリは何らかの遺伝子変異を有する定型RP患者100例を対象とする前向き多施設研究であり、20～70歳、Humphrey 10-2視野検査において中心点12ヶ所の平均網膜感度が10dB以上、OCT所見における中心窩網膜厚250μm以下、眼合併症や全身性合併症を有さないことをレジストリ登録の選定基準とし、除外基準はヘモグロビン値8g/dL以下の貧血、全身状態不良、緑内障または眼圧亢進、ブドウ膜炎または視神経炎とする。RPの疾患増悪の評価として視力検査、Humphrey 10-2視野検査、OCT検査、眼底自己蛍光画像検査を3ヵ月ごとに行い、炎症性パラメータとして房水フレア値、高感度CRP、血清中IL-8、CD14/16炎症性単球比率を測定する。主要評価項目はHumphrey 10-2視野検査における網膜感受性欠失の増悪率、副次評価項目は視力検査、OCT検査および眼底自己蛍光画像検査の各所見の増悪率と炎症性パラメータとの関連とする。本レジストリがRPに対する抗炎症治療のプロトコル作成の一助となることが期待される。
Study protocol for a prospective natural history registry investigating the relationships between inflammatory markers and disease progression in retinitis pigmentosa: the RP-PRIMARY study. Reviewed International journal

Yusuke Murakami, Takahiro Hisai, Sakurako Shimokawa, Masatoshi Fukushima, Kohta Fujiwara, Akie Hirata, Atsushi Takada, Fuyuka Miyahara, Naoki Nakashima, Yuko Kobayakawa, Mitsuru Arima, Go Mawatari, Masataka Ishizu, Tomoko Kaida, Kazunori Miyata, Yasuhiro Ikeda, Koh-Hei Sonoda

Japanese journal of ophthalmology 69 ( 3 ) 378 - 386 2025.5 （ ISSN:0021-5155 eISSN:1613-2246 ）

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Language：English Publishing type：Research paper (scientific journal) Publisher：Japanese Journal of Ophthalmology

PURPOSE: The Retinitis Pigmentosa Progression and Inflammatory Marker Registry (RP-PRIMARY) is intended as a prospective observational study aimed at establishing sensitive outcome measures to detect the efficacy of anti-inflammatory agents in future clinical trials. The following is the RP-PRIMARY study protocol. STUDY DESIGN: Prospective, multicenter study. METHODS: We will recruit 100 patients with typical RP (any genetic mutation) and the following characteristics: age 20-70 years; mean retinal sensitivity ≥ 10 dB at 12 central points on Humphrey 10-2 visual field tests; central foveal thickness ≤ 250 μm on optical coherence tomography (OCT); and no ocular complications unrelated to RP or serious systemic complications. Early Treatment Diabetic Retinopathy Study (ETDRS). visual acuity, Humphrey 10-2 visual field tests, OCT, and fundus autofluorescence imaging will be performed every 3 months for 2 years. Inflammatory indices such as aqueous flare values, high-sensitivity C-reactive protein (CRP), serum IL-8, and CD14/16 inflammatory monocyte proportion will be measured every year. The primary endpoint will be the progression rate of retinal sensitivity loss on the Humphrey 10-2 visual field tests. The secondary endpoints will be the rate of decline of each parameter and its association with inflammatory indices. Standard-operation-procedure documents were prepared for all study procedures, and consultations with the regulatory agency were conducted to ensure the data reliability for future use in clinical trials. CONCLUSIONS: Detailed registry data on the natural history and inflammatory profile of RP will be useful in designing study protocols for anti-inflammatory therapy for RP and as natural history data for drug applications.

DOI： 10.1007/s10384-025-01179-2

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Heterotypic macrophages/microglia differentially contribute to retinal ischaemia and neovascularisation. Reviewed International coauthorship International journal

Muneo Yamaguchi, Shintaro Nakao, Mitsuru Arima, Karis Little, Aditi Singh, Iori Wada, Yoshihiro Kaizu, Souska Zandi, Justus G Garweg, Tetsuya Matoba, Wataru Shiraishi, Ryo Yamasaki, Kensuke Shibata, Yasuhiro Go, Tatsuro Ishibashi, Akiyoshi Uemura, Alan W Stitt, Koh-Hei Sonoda

Diabetologia 67 ( 10 ) 2329 - 2345 2024.10 （ ISSN:0012-186X eISSN:1432-0428 ）

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Language：English Publishing type：Research paper (scientific journal) Publisher：Diabetologia

AIMS/HYPOTHESIS: Diabetic retinopathy is characterised by neuroinflammation that drives neuronal and vascular degenerative pathology, which in many individuals can lead to retinal ischaemia and neovascularisation. Infiltrating macrophages and activated retina-resident microglia have been implicated in the progression of diabetic retinopathy, although the distinct roles of these immune cells remain ill-defined. Our aim was to clarify the distinct roles of macrophages/microglia in the pathogenesis of proliferative ischaemic retinopathies. METHODS: Murine oxygen-induced retinopathy is commonly used as a model of ischaemia-induced proliferative diabetic retinopathy (PDR). We evaluated the phenotype macrophages/microglia by immunostaining, quantitative real-time RT-PCR (qRT-PCR), flow cytometry and scRNA-seq analysis. In clinical imaging studies of diabetic retinopathy, we used optical coherence tomography (OCT) and OCT angiography. RESULTS: Immunostaining, qRT-PCR and flow cytometry showed expression levels of M1-like macrophages/microglia markers (CD80, CD68 and nitric oxide synthase 2) and M2-like macrophages/microglia markers (CD206, CD163 and macrophage scavenger receptor 1) were upregulated in areas of retinal ischaemia and around neo-vessels, respectively. scRNA-seq analysis of the ischaemic retina revealed distinct ischaemia-related clusters of macrophages/microglia that express M1 markers as well as C-C chemokine receptor 2. Inhibition of Rho-kinase (ROCK) suppressed CCL2 expression and reduced CCR2-positive M1-like macrophages/microglia in areas of ischaemia. Furthermore, the area of retinal ischaemia was reduced by suppressing blood macrophage infiltration not only by ROCK inhibitor and monocyte chemoattractant protein-1 antibody but also by GdCl3. Clinical imaging studies of diabetic retinopathy using OCT indicated potential involvement of macrophages/microglia represented by hyperreflective foci in areas of reduced perfusion. CONCLUSIONS/INTERPRETATION: These results collectively indicated that heterotypic macrophages/microglia differentially contribute to retinal ischaemia and neovascularisation in retinal vascular diseases including diabetic retinopathy. This adds important new information that could provide a basis for a more targeted, cell-specific therapeutic approach to prevent progression to sight-threatening PDR.

DOI： 10.1007/s00125-024-06215-3

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未熟児網膜症を有する早産児に対するリパスジル点眼剤の安全性と有効性　第I/II相オープン単群試験(Safety and efficacy of ripasudil eye drops in preterm infants with retinopathy of prematurity: phase 1/2, open label, single-arm trial) Reviewed International journal

Arima Mitsuru, Inoue Hirosuke, Misumi Akiko, Tsukamoto Shoko, Matsushita Itsuka, Araki Shunsuke, Ohta Manami, Takahashi Kazumasa, Imazato Miyuki, Goto Tomoko, Aoki Yoshinori, Tagawa Koshiro, Hirose Masayuki, Fujita Yuito, Yoshida Noriko, Nakao Shintaro, Kondo Hiroyuki, Kusuhara Koichi, Kimura Kazuhiro, Hasegawa Shunji, Ikeda Yasuhiro, Kodama Yuki, Moritake Hiroshi, Ochiai Masayuki, Ohga Shouichi, Kishimoto Junji, Todaka Koji, Ieiri Ichiro, Sonoda Koh-hei

Japanese Journal of Ophthalmology 68 ( 5 ) 490 - 499 2024.9 （ ISSN:0021-5155 ）

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Language：English Publishing type：Research paper (scientific journal) Publisher：シュプリンガー・ジャパン(株)

未熟児網膜症(ROP)に対するリパスジル点眼剤の安全性と有効性を検討した。Zone I・IIにステージ1以上のROPを呈する在胎32週以下または体重1500g未満の早産児24例(男児14例、女児10例、平均在胎週数25.2±1.6)を対象に、第I/II相多施設オープン単群12週試験を行った。第I相試験ではリパスジル点眼剤の用量漸増試験を実施し、1週目は1日1回投与、2週目は1日投与とし、安全性に問題がみられなければ最長9週まで継続した。第II相試験では最長12週、1日2回投与とし、安全性を評価するとともに、1型ROPへの増悪率、無増悪期間、ROPの進行度を検討した。第I相試験の完遂例は15例、リパスジルの投与中止は9例[1型ROPへの増悪7例、投与不同意1例、侵襲性後部(AP)-ROPへの増悪1例]であった。全身性有害事象(AEs)の発現を19例(79.2%)に53件認め、このうち重篤例は5例(20.8%)7件であったが、AEsとリパスジルとの明確な因果関係はないと判定された。有効性に関して、1型ROPへの増悪率にリパスジル投与群と既存対照群84例(男児48例、女児36例、平均在胎週数26.9±2.3)との間に有意差はみられなったが、在胎27週以下の患児に限定すると増悪率はリパスジル群の方が有意に低値を示していた。特に在胎週数が短いROPに対してリパスジルは有効であることが示された。
Natural History and its Association with Inflammatory Markers in Retinitis Pigmentosa: The Protocol of RP PRIMARY Study Reviewed International journal

Murakami, Y; Shimokawa, S; Fukushima, M; Hirose, A; Fujiwara, K; Hirata, A; Takada, A; Tokunaga, S; Kobayakawa, Y; Arima, M; Kaida, T; Miyata, K; Mawatari, G; Ishizu, M; Ikeda, Y; Sonoda, KH

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 64 ( 8 ) 2023.6 （ ISSN:0146-0404 eISSN:1552-5783 ）

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VOLUMETRIC THREE-DIMENSIONAL OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF RETINAL NEOVASCULARIZATION IN PROLIFERATIVE DIABETIC RETINOPATHY. Reviewed International journal

Shintaro Nakao, Yoshihiro Kaizu, Juun Horie, Iori Wada, Mitsuru Arima, Yosuke Fukuda, Keijiro Ishikawa, Koh-Hei Sonoda

Retinal cases & brief reports 17 ( 3 ) 315 - 320 2023.5 （ ISSN:19351089 ）

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Language：English Publishing type：Research paper (scientific journal) Publisher：Retinal Cases and Brief Reports

PURPOSE: To evaluate structural and angiographic neovascularization in patients with proliferative diabetic retinopathy using volumetric three-dimensional optical coherence tomography angiography (OCTA). METHODS: This prospective, observational cross-sectional study included 29 eyes of 27 patients with proliferative diabetic retinopathy. The angiogenic structure, feeding vessel (epicenter), flow volume, and flow volume density of the neovasculatures were evaluated using three-dimensional OCTA imaging. The flow area and the flow area density were also measured using en face OCTA imaging. RESULTS: Sites of neovascularization were imaged successfully in 17 of the 29 eyes (58.6%). Three proposed types of neovascularization were identified on the basis of structural features seen on the three-dimensional OCTA images. Neovascularization of the adhesion type (9 of 17, 52.9%) adhered to the retinal vasculature. Those of the traction type (5 of 17, 29.4%) were partially separated from the retinal vascular plexus. Those of the mushroom type (3 of 17, 17.6%) were connected to the retinal vasculature by several epicenters. There was a significant difference between highly leaky (active) and faintly leaky (inactive) neovascularization for flow volume density, but not for flow area, flow volume, or flow area density ( P = 0.01, 0.9, 0.6, and 0.1, respectively). CONCLUSION: Volumetric three-dimensional OCTA revealed three types of neovascularization in proliferative diabetic retinopathy and may be useful for assessing neovascular activity and planning vitrectomies.

DOI： 10.1097/ICB.0000000000001183

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Rhodopsin-positive cell production by intravitreal injection of small molecule compounds in mouse models of retinal degeneration. Reviewed International journal

Yuya Fujii, Mitsuru Arima, Yusuke Murakami, Koh-Hei Sonoda

PloS one 18 ( 2 ) e0282174 2023.2 （ ISSN:1932-6203 ）

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Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Plos One

We aimed to verify whether the intravitreal injection of small molecule compounds alone can create photoreceptor cells in mouse models of retinal degeneration. Primary cultured mouse Müller cells were stimulated in vitro with combinations of candidate compounds and the rhodopsin expression was measured on day 7 using polymerase chain reaction and immunostaining. We used 6-week-old N-methyl-N-nitrosourea-treated and 4-week-old rd10 mice as representative in vivo models of retinal degeneration. The optimal combination of compounds selected via in vitro screening was injected into the vitreous and the changes in rhodopsin expression were investigated on day 7 using polymerase chain reaction and immunostaining. The origin of rhodopsin-positive cells was also analyzed via lineage tracing and the recovery of retinal function was assessed using electroretinography. The in vitro mRNA expression of rhodopsin in Müller cells increased 30-fold, and 25% of the Müller cells expressed rhodopsin protein 7 days after stimulation with a combination of 4 compounds: transforming growth factor-β inhibitor, bone morphogenetic protein inhibitor, glycogen synthase kinase 3 inhibitor, and γ-secretase inhibitor. The in vivo rhodopsin mRNA expression and the number of rhodopsin-positive cells in the outer retina were significantly increased on day 7 after the intravitreal injection of these 4 compounds in both N-methyl-N-nitrosourea-treated and rd10 mice. Lineage tracing in td-Tomato mice treated with N-methyl-N-nitrosourea suggested that the rhodopsin-positive cells originated from endogenous Müller cells, accompanied with the recovery of the rhodopsin-derived scotopic function. It was suggested that rhodopsin-positive cells generated by compound stimulation contributes to the recovery of retinal function impaired by degeneration.

DOI： 10.1371/journal.pone.0282174

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Identifying Hyperreflective Foci in Diabetic Retinopathy via VEGF-Induced Local Self-Renewal of CX3CR1+ Vitreous Resident Macrophages. Reviewed International coauthorship International journal

Muneo Yamaguchi, Shintaro Nakao, Iori Wada, Tetsuya Matoba, Mitsuru Arima, Yoshihiro Kaizu, Mariko Shirane, Keijiro Ishikawa, Takahito Nakama, Yusuke Murakami, Masaharu Mizuochi, Wataru Shiraishi, Ryo Yamasaki, Toshio Hisatomi, Tatsuro Ishibashi, Masabumi Shibuya, Alan W Stitt, Koh-Hei Sonoda

Diabetes 71 ( 12 ) 2685 - 2701 2022.12 （ ISSN:0012-1797 eISSN:1939-327X ）

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Language：English Publishing type：Research paper (scientific journal) Publisher：Diabetes

Intraretinal hyperreflective foci (HRF) are significant biomarkers for diabetic macular edema. However, HRF at the vitreoretinal interface (VRI) have not been examined in diabetic retinopathy (DR). A prospective observational clinical study with 162 consecutive eyes using OCT imaging showed significantly increased HRF at the VRI during DR progression (P < 0.01), which was reversed by anti-vascular endothelial growth factor (VEGF) therapy. F4/80+ macrophages increased significantly at the VRI in Kimba (vegfa+/+) or Akimba (Akita × Kimba) mice (both P < 0.01), but not in diabetic Akita (Ins2+/-) mice, indicating macrophage activation was modulated by elevated VEGF rather than the diabetic milieu. Macrophage depletion significantly reduced HRF at the VRI (P < 0.01). Furthermore, BrdU administration in Ccr2rfp/+Cx3cr1gfp/+vegfa+/- mice identified a significant contribution of M2-like tissue-resident macrophages (TRMs) at the VRI. Ki-67+ and CD11b+ cells were observed in preretinal tissues of DR patients, while exposure of vitreal macrophages to vitreous derived from PDR patients induced a significant proliferation response in vitro (P < 0.01). Taken together, the evidence suggests that VEGF drives a local proliferation of vitreous resident macrophages (VRMs) at the VRI during DR. This phenomenon helps to explain the derivation and disease-relevance of the HRF lesions observed through OCT imaging in patients.

DOI： 10.2337/db21-0247

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Morphology and fluorescein leakage in diabetic retinal microaneurysms: a study using multiple en face OCT angiography image averaging. Reviewed International journal

Yosuke Fukuda, Shintaro Nakao, Yoshihiro Kaizu, Mitsuru Arima, Sakurako Shimokawa, Iori Wada, Muneo Yamaguchi, Atsunobu Takeda, Koh-Hei Sonoda

Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 260 ( 11 ) 3517 - 3523 2022.11 （ ISSN:0721-832X eISSN:1435-702X ）

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Language：English Publishing type：Research paper (scientific journal) Publisher：Graefe S Archive for Clinical and Experimental Ophthalmology

PURPOSE: To investigate the relevance of microaneurysm morphology in optical coherence tomography angiography (OCTA) image averaging and fluorescein leakage in diabetic retinopathy (DR). METHODS: In 38 consecutive patients with DR, ten consecutive 3- × 3-mm fovea-centered OCTA (HS100, Canon Inc., Tokyo, Japan) and fluorescein angiography (FA) were performed, and averaged OCTA images were created based on the 10 images. After detecting all microaneurysms in FA images, the morphology was classified into four types (focal bulge, saccular/pedunculated, fusiform, and mixed) using averaged OCTA images. The correlation between microaneurysm leakage in FA, retinopathy stage, and microaneurysm morphology was estimated. RESULTS: Thirty-eight eyes (50.0%) of the 33 patients were available for analysis, and 370 (63.5%) of the 583 FA-detected microaneurysms were morphologically classifiable (focal bulge, 46; saccular/pedunculated, 143; fusiform, 29; and mixed, 152) in OCTA. There was a significant correlation between stage and percentage of microaneurysm morphology and between morphology and the presence of leakage (P < 0.0001 and P < 0.01, respectively). The proportion of focal bulges decreased with stage progression, while the other three types increased with stage progression. The percentage of FA leakage for focal bulge, saccular/pedunculated, fusiform, and mixed was 41.3%, 66.4%, 82.8%, and 66.4%, respectively, and the fusiform type showed significant FA leakage. CONCLUSION: Microaneurysm morphology is correlated with the DR stage and FA leakage. Microaneurysm morphology recognition using OCTA image averaging may be useful for the clinical evaluation of DR.

DOI： 10.1007/s00417-022-05713-7

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Hyperreflective Membrane at the Vitreoretinal Interface in Diabetic Macular Edema: A Finding in Ultra-High-Resolution Optical Coherence Tomography. Reviewed International coauthorship International journal

Iori Wada, Shintaro Nakao, Mitsuru Arima, Keijiro Ishikawa, Muneo Yamaguchi, Yoshihiro Kaizu, Haruka Sekiryu, Kenichiro Mori, Kohei Kiyohara, Atsunobu Takeda, Tatsuro Ishibashi, SriniVas R Sadda, Koh-Hei Sonoda

Translational vision science & technology 11 ( 9 ) 21 - 21 2022.9 （ ISSN:2164-2591 ）

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Language：English Publishing type：Research paper (scientific journal) Publisher：Translational Vision Science and Technology

PURPOSE: Detecting subtle vitreoretinal interface (VRI) findings, such as a posterior hyaloid membrane, is difficult with conventional retinal imaging. We compared ultra-high-resolution spectral domain optical coherence tomography (UHR-SD-OCT) with standard-resolution OCT (SD-OCT) for the imaging of VRI abnormalities in diabetic retinopathy (DR). METHODS: This prospective cross-sectional study included 113 consecutive patients (91 patients with diabetes and 22 healthy controls). The VRI was evaluated, and the results were compared between the conventional SD-OCT and UHR-SD-OCT images. VRI findings were also investigated before and after internal limiting membrane peeling during vitrectomy for proliferative DR. RESULTS: A total of 159 eyes (87.4%) of 91 patients with diabetes were analyzed. UHR-SD-OCT could detect a hyperreflective layer at the VRI, in which en face OCT showed a membrane-like structure, termed the hyperreflective membrane (HRMe). The preoperative HRMe could not be detected in all patients with proliferative DR who underwent internal limiting membrane peeling during vitrectomy. Although the HRMe did not correlate with the DR stage, eyes with diabetic macular edema (DME) (64.5%) showed a significant HRMe with UHR-SD-OCT more frequently than those without DME (35.8%) (P = 0.005). CONCLUSIONS: UHR-SD-OCT can detect the HRMe at the VRI in DR eyes, particularly in eyes with DME. The HRMe may present a thickened posterior hyaloid membrane that contributes to DME development. TRANSLATIONAL RELEVANCE: UHR-SD-OCT detects slight changes in the VRI in DR eyes. In the future, it may help to elucidate the mechanism of DME formation.

DOI： 10.1167/tvst.11.9.21

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ブタの膵尾部切除に用いられる新規生体吸収性膵臓クリップの有効性(Efficacy of a newly developed bioabsorbable pancreatic clip for distal pancreatectomy in swine) Reviewed International journal

Yamashita Yo-ichi, Yamao Takanobu, Nakao Yosuke, Miyata Tatsunori, Ikegami Yasuhiro, Yamane Soichiro, Ito Taiga, Furukawa Taku, Cho Jaeyong, Wu Fanqi, Fujie Yasumitsu, Arima Mitsuru, Aishima Shinichi, Ijima Hiroyuki, Baba Hideo

Surgery Today 52 ( 7 ) 1109 - 1114 2022.7 （ ISSN:0941-1291 ）

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Language：English Publishing type：Research paper (scientific journal) Publisher：シュプリンガー・ジャパン(株)

膵尾部切除に際して膵断端閉塞中に膵実質を破断させないようなポリカプロラクトン製の新規生体吸収性膵臓クリップ(BioPaC)を作製し、その有効性を検討した。体重25～30kgの健常ブタを用いて実験を行い、手術では膵尾部を脾静脈と後腹膜から切離した後、脾膵葉の最も厚みのある部分を、BioPaCを用いて閉鎖した。対照にはReinforceを用いてBioPaCと同様の処理を施した。BioPaCは長さ59mm、高さ6mm、厚み5mm、クランプ時の幅16mm、クランプ時のギャップ4mmという構造であった。Reinforceを使用したブタ2匹のうち1匹は術後7日目に死亡し、グレードCの術後膵液漏(POPF)と診断された。もう1匹は術後30日まで生存したが、膵断端周囲に著明な腹腔内癒着が観察された。BioPaCを用いた3匹の術後経過は良好で、POPFの発症は認められなかった。病理学的所見ではBioPaCによって主膵管と膵実質の閉鎖が得られていた。ブタ膵尾部切除モデルにおいてBioPaCは有効であることが示された。
Mucosal-associated invariant T cells have therapeutic potential against ocular autoimmunity. Reviewed International journal

Satoshi Yamana, Kensuke Shibata, Eiichi Hasegawa, Mitsuru Arima, Shotaro Shimokawa, Nobuyo Yawata, Atsunobu Takeda, Sho Yamasaki, Koh-Hei Sonoda

Mucosal immunology 15 ( 2 ) 351 - 361 2022.2 （ ISSN:1933-0219 eISSN:1935-3456 ）

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Language：English Publishing type：Research paper (scientific journal) Publisher：Mucosal Immunology

Autoimmune uveitis is a sight-threatening disease induced by pathogenic T cells that recognize retinal antigens; it is observed in disorders including Vogt-Koyanagi-Harada disease (VKH). The roles of specific T cell subsets and their therapeutic potential against autoimmune uveitis are not fully understood. Here we conducted multi-parametric single-cell protein quantification which shows that the frequency of CD161highTRAV1-2+ mucosal-associated invariant T (MAIT) cells that recognize vitamin B2 metabolite-based antigens is decreased in relapsing VKH patients compared to individuals without active ocular inflammation. An experimental autoimmune uveitis (EAU) mouse model revealed that genetic depletion of MAIT cells reduced the expression of interleukin (Il) 22 and exacerbated retinal pathology. Reduced IL-22 levels were commonly observed in patients with relapsing VKH compared to individuals without active ocular inflammation. Both mouse and human MAIT cells produced IL-22 upon stimulation with their antigenic metabolite in vitro. An intravitreal administration of the antigenic metabolite into EAU mice induced retinal MAIT cell expansion and enhanced the expressions of Il22, as well as its downstream genes related to anti-inflammatory and neuroprotective effects, leading to an improvement in both retinal pathology and visual function. Taken together, we demonstrate that a metabolite-driven approach targeting MAIT cells has therapeutic potential against autoimmune uveitis.

DOI： 10.1038/s41385-021-00469-5

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Microaneurysm Imaging using Multiple En Face Optical Coherence Tomography Angiography Image Averaging: Morphology and Visualization Invited Reviewed International journal

@Yoshihiro Kaizu,@Shintaro Nakao,@Iori Wada,@Mitsuru Arima,@Muneo Yamaguchi,@Keijiro Ishikawa,@Masato Akiyama,@Junji Kishimoto,@Toshio Hisatomi,@Koh-Hei Sonoda

Ophthalmology Retina. 2019.9

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調節麻痺屈折検査後に閉塞隅角緑内障を発症した小児網膜疾患の2例 Reviewed

#石龍悠,@村上祐介,@有馬充,@塚本晶子,@池田康博,@園田康平

あたらしい眼科３６ ( 8 ) 1065 - 1069 2019.8

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Flow Density in Optical Coherence Tomography Angiography is Useful for Retinopathy Diagnosis in Diabetic Patients Reviewed International journal

@Yoshihiro Kaizu,@Shintaro Nakao,@Mitsuru Arima,@Takehito Hayami,@Iori Wada,@Muneo Yamaguchi,@Haruka Sekiryu,@Keijiro Ishikawa,@Yasuhiro Ikeda,@Koh-Hei Sonoda

Sci Rep. 9 ( 1 ) 8668 2019.6

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The utility of a new fundus camera using a portable slit lamp combined with a smartphone. Reviewed International journal

@Arima M,@Majima T,@Tsukamoto S,@Hara T,@Wada I,@Nakao S,@Sonoda KH

Acta Ophthalmol. 2019.2

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Ocular findings in a case of Pierson syndrome with a novel mutation in laminin ß2 gene. Reviewed International journal

@Arima M,@Tsukamoto S,@Akiyama R,@Nishiyama K,@Kohno RI,@Tachibana T,@Hayashida A,@Murayama M,@Hisatomi T,@Nozu K,@Iijima K,@Ohga S,@Sonoda KH

J AAPOS 2018.10

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Crucial role of P2X7 receptor for effector T cell activation in experimental autoimmune uveitis. Invited Reviewed International journal

Takeda A, Yamada H, @Hasegawa E, @Arima M, @Notomi S, Myojin S, Yoshimura T, @Hisatomi T, Enaida H, Yanai R, Kimura K, @Ishibashi T, @Sonoda KH.

Jpn J Ophthalmol. 2018.3

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Interleukin-6 plays a crucial role in the development of subretinal fibrosis in a mouse model. Reviewed International journal

@Sato K,@Takeda A,@Hasegawa E,@Jo YJ,@Arima M,@Oshima Y,@Ryoji Y,@Nakazawa T,@Yuzawa M,@Nakashizuka H,@Shimada H,@Kimura K,@Ishibashi T,@Sonoda KH

Immunol Med 2018.3

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Optical Coherence Tomography Angiography Reveals Spatial Bias of Macular Capillary Dropout in Diabetic Retinopathy. Invited Reviewed International journal

Kaizu Y, @Nakao S, Yoshida S, Hayami T, @Arima M, Yamaguchi M, Wada I, @Hisatomi T, @Ikeda Y, @Ishibashi T, @Sonoda KH.

Invest Ophthalmol Vis Sci. 2017.9

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Tenascin-C secreted by transdifferentiated retinal pigment epithelial cells promotes choroidal neovascularization via integrin αV. Invited Reviewed International journal

Kobayashi Y, Yoshida S, Zhou Y, Nakama T, @Ishikawa K, Kubo Y, @Arima M, @Nakao S, @Hisatomi T, @Ikeda Y, Matsuda A, @Sonoda KH, @Ishibashi T.

Lab Invest. 2016.11

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High-Resolution Imaging by Adaptive Optics Scanning Laser Ophthalmoscopy Reveals Two Morphologically Distinct Types of Retinal Hard Exudates. Invited Reviewed International journal

Yamaguchi M, @Nakao S, Kaizu Y, Kobayashi Y, Nakama T, @Arima M, Yoshida S, Oshima Y, Takeda A, @Ikeda Y, Mukai S, @Ishibashi T, @Sonoda KH.

Sci Rep. 2016.9

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Tenascin-C promotes angiogenesis in fibrovascular membranes in eyes with proliferative diabetic retinopathy. Invited Reviewed International journal

Kobayashi Y, Yoshida S, Zhou Y, Nakama T, @Ishikawa K, @Arima M, @Nakao S, Sassa Y, Takeda A, @Hisatomi T, @Ikeda Y, Matsuda A, @Sonoda KH, @Ishibashi T.

Mol Vis. 2016.4

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Antiangiogenic shift in vitreous after vitrectomy in patients with proliferative diabetic retinopathy. Invited Reviewed International journal

Yoshida S, Nakama T, @Ishikawa K, @Arima M, Tachibana T, @Nakao S, Sassa Y, Yasuda M, Enaida H, Oshima Y, Kono T, @Ishibashi T.

Invest Ophthalmol Vis Sci. 2012.10

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Post-treatment change in the localization of recurrent or persistent macular edema secondary to branch retinal vein occlusion. Invited Reviewed International journal

@Arima M, Miyazaki M, Arakawa S, Mochizuki Y, @Ishibashi T.

Ophthalmologica. 2012.5

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Bone marrow-derived monocyte lineage cells recruited by MIP-1β promote physiological revascularization in mouse model of oxygen-induced retinopathy. Invited Reviewed International journal

@Ishikawa K, Yoshida S, @Nakao S, Sassa Y, Asato R, Kohno R, @Arima M, Kita T, Yoshida A, Ohuchida K, @Ishibashi T.

Lab Invest. 2012.1

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Increased expression of periostin in vitreous and fibrovascular membranes obtained from patients with proliferative diabetic retinopathy. Invited Reviewed International journal

Yoshida S, @Ishikawa K, Asato R, @Arima M, Sassa Y, Yoshida A, Yoshikawa H, Narukawa K, Obika S, Ono J, Ohta S, Izuhara K, Kono T, @Ishibashi T.

Invest Ophthalmol Vis Sci. 2011.7

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A case of metastatic choroidal tumor simulating a choroidal melanoma. Invited Reviewed International journal

@Arima M, Yoshikawa H, Kagimoto T, @Kohno RI, @Ishibashi T.

Jpn J Ophthalmol. 2011.5

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An early "reopening" case of idiopathic macular hole; supportive usefulness of fundus autofluorescence. Invited Reviewed International journal

@Arima M, Miyazaki M, @Kohno R, Hata Y, @Ishibashi T.

Graefes Arch Clin Exp Ophthalmol. 2009.5

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Books

組織低酸素状態における血液脳関門機能異常

@有馬　充, 崔　丹, 池田　栄二

血管医学 2014.3

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Acute Retinal Necrosis and Progressive Outer Retinal Necrosis

@Atsunobu Takeda,@Mitsuru Arima,@Keijiro Ishikawa,@Eiichi Hasegawa,@Yusuke Murakami,@Koh-Hei Sonoda（Role：Joint author）

Inflammatory and Infectious Ocular Disorders 2019.11

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Responsible for pages：215-220 Language：English Book type：Scholarly book

Presentations

未熟児網膜症に対するリパスジル点眼多施設共同第Ⅰ/Ⅱ相医師主導治験 Invited

有馬充

第46回日本小児眼科学会総会. 2021.6
Current challenges in pediatric drug development Invited

Mitsuru Arima

第130回日本眼科学会総会. 2026.4
ドラッグ・ロス解消に向けた国及びPMDAの取り組み Invited

有馬充

第45回日本眼薬理学会 2025.11
新生児医療における医師主導治験の経験 Invited

有馬充

第67回日本新生児成育医学会・学術集会. 2023.11
ベバシズマブ硝子体注射を受けた未熟児網膜症患児の中枢神経発達

#森雄二郎,@有馬充,@秋山雅人,@藤原康太,@井上普介,@関瑛子,@中間崇仁,@塚本晶子,@落合正行,@大賀正一,@園田康平

日本眼科学会総会 2020.4

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Event date： 2020.6

Language：Japanese Presentation type：Oral presentation (general)

Country：Japan
網膜光凝固後の未熟児網膜症患児における1歳時の屈折値関連因子

#森雄二郎,@有馬充,@上田瑛美,@塚本晶子,@藤原康太,@秋山雅人,@園田康平

日本小児眼科学会総会 2019.6

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Event date： 2020.6

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内頸動脈ステント留置術後に血管新生緑内障が増悪した眼虚血症候群の1例

#森賢一郎,@武田篤信,@納富昭司,@有馬充,@石川桂二郎,@園田康平

日本眼循環学会 2019.7

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Event date： 2020.6

Language：Japanese Presentation type：Oral presentation (general)

Country：Japan
加算平均OCT angiographyを用いた糖尿病網膜症における毛細血管瘤の形態解析

@福田洋輔,@中尾新太郎,@海津嘉弘,@有馬充,@和田伊織,@山口宗男,@秋山雅人,@石川桂二郎,@下川桜子,@園田康平

日本眼循環学会 2019.7

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Event date： 2020.6

Language：Japanese

Country：Japan
Refractive outcomes after laser photocoagulation for retinopathy of prematurity International conference

#Yujiro Mori,@Mitsuru Arima,@Emi Ueda E,@Kohta Fujiwara,@Shoko Tsukamoto,@Masato Akiyama,@Koh-Hei Sonoda

The 12th Joint Meeting of Chinese-Japanese-Korean Ophthalmologist 2019.9

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Event date： 2020.6

Language：English Presentation type：Oral presentation (general)

Country：China
Microaneurysm Imaging using Multiple En Face OCTA Image Averaging: Morphology and Visualization International conference

@Shintaro Nakao,@Yoshihiro Kaizu,@Iori Wada,@Mitsuru Arima,@Muneo Yamaguchi,@Keijiro Ishikawa,@Masato Akiyama,@Koh-Hei Sonoda

Retina Society Meeting 2019.9

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Event date： 2020.6

Language：English

Country：United Kingdom
糖尿病網膜症における血管透過性亢進が網膜感度に及ぼす影響

@有馬充,@中尾新太郎,@海津嘉弘,@和田伊織,@山口宗男,@藤原康太,@園田康平

日本糖尿病眼学会総会 2019.9

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Event date： 2020.6

Language：Japanese

Country：Japan
超高分解能OCTによるDME網膜硝子体界面所見と抗VEGF療法反応性の検討

@和田伊織,@中尾新太郎,@有馬充,@海津嘉弘,@山口宗男,@石川桂二郎,@園田康平

日本臨床眼科学会 2019.10

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Event date： 2020.6

Language：Japanese Presentation type：Oral presentation (general)

Country：Japan
OCT angiographyにおけるInterscan time変更による網膜血管検出能の検討

@海津嘉弘,@中尾新太郎,@有馬充,@和田伊織,@山口宗男,@森賢一郎,@秋山雅人,@石川桂二郎,@園田康平

日本網膜硝子体学会総会 2019.12

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Event date： 2020.6

Language：Japanese

Country：Japan
AMDにおける抗VEGF療法後のCNV消退メカニズム

@和田伊織,@中尾新太郎,@海津嘉弘,@山口宗男,@森賢一郎,@石川桂二郎,@有馬充,@塩瀬聡美,@園田康平

日本眼科学会総会 2020.4

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Event date： 2020.6

Language：Japanese Presentation type：Oral presentation (general)

Country：Japan
ROCK inhibitor Ripasudil reverses phenotype from EMT to MET in subretinal fibrosis International conference

@Iori Wada,@Shintaro Nakao,@Muneo Yamaguchi,@Mitsuru Arima,@Ken-ichiro Mori,@Yoshihiro kaizu,@Tatsuro Ishibashi,@Koh-Hei Sonoda

Association for Research in Vision and Ophthalmology 2019.5

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Event date： 2019.4 - 2019.5

Language：English Presentation type：Symposium, workshop panel (public)

Venue：Vancouver Country：Canada
The direct reprogramming of retinal astrocytes into neurons with small-molecule compounds International conference

@Yuya Fujii,@Mitsuru Arima,@Shotaro Shimokawa,@Yusuke Murakami,@Koh-Hei Sonoda

The Association for Research in Vision and Ophthalmology 2019.5

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Event date： 2019.4 - 2019.5

Language：English Presentation type：Symposium, workshop panel (public)

Venue：Vancouver Country：Canada
A photographing device for ocular fundus and fluorescein angiography using a portable slit lamp International conference

@Misturu Arima,@Takuya Majima,@Shoko Tsukamoto,@Takuya Hara,@Iori Wada,@Shintaro Nakao,@Koh-Hei Sonoda

The Association for Research in Vision and Ophthalmology 2019.4

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Event date： 2019.4 - 2019.5

Language：English Presentation type：Symposium, workshop panel (public)

Venue：Vancouver Country：Canada
Local Proliferation of CD206+ CX3CR1+ Macrophages at the Vitreoretinal Interface in Diabetic Retinopathy International conference

@Shintaro Nakao,@Muneo Yamaguchi,@Iori Wada,@Yoshihiro Kaizu,@Mitsuru Arima,@Keijiro Ishikawa,@Takahito Nakama,@Wataru Shiraishi,@Ryo Tamasaki,@Jun-ichi Kiram,@Tatsuro Ishibashi,@Koh-Hei Sonoda

Association of Research in Vision and Ophthalmology 2019.5

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Event date： 2019.4 - 2019.5

Language：English Presentation type：Symposium, workshop panel (public)

Venue：Vancouver Country：Canada
Measurement of Vessel Tortuosity in Epiretinal Membrane in Optical Coherence Tomography Angiography International conference

@Haruka Sekiryu,@Shintaro nakao,@Hayami T,@Yoshihiro Kaizu,@Iori Wada,@Mitsuru Arima,@Keijiro Ishikawa,@Higashijima N,@Morooka K,@Koh-Hei Sonoda

Association of Research in Vision and Ophthalmology 2019.4

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Event date： 2019.4 - 2019.5

Language：English Presentation type：Symposium, workshop panel (public)

Venue：Vancouver Country：Canada
Proximal but not distal retinal ischemia is associated with microaneurysms in diabetic retinopathy International conference

@Yoshihiro Kaizu,@Shintaro Nakao,@Mitsuru Arima,@Iori Wada,@Muneo Yamaguchi,@Masato Akiyama,@Keijiro Ishikawa,@Koh-Hei Sonoda

The Association for Research in Vision and Ophthalmology 2019.5

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Event date： 2019.4 - 2019.5

Language：English Presentation type：Symposium, workshop panel (public)

Venue：Vancouver Country：Canada
Novel predictors of treatment-requiring retinopathy of prematurity Invited

@Mitsuru Arima

日本眼科学会総会 2019.4

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Event date： 2019.4

Language：English Presentation type：Symposium, workshop panel (public)

Venue：東京都 Country：Japan
ポータブルスリットランプとスマートフォンを用いた眼底写真撮影と蛍光眼底造影

@有馬充,@眞島拓也,@塚本晶子,@原拓也,@和田伊織,@中尾新太郎,@園田　康平

日本眼科学会総会 2019.4

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Event date： 2019.4

Language：Japanese Presentation type：Symposium, workshop panel (public)

Venue：東京都 Country：Japan
糖尿病網膜症におけるCD206+CX3CR1+ 硝子体界面マクロファージ局所増殖

@山口　宗男,@中尾　新太郎,@和田　伊織,@海津　嘉弘,@有馬　充,@石川　桂二郎,@中間　崇仁,@白石　渉,@山崎　亮,@吉良　潤一,@石橋　達朗,@園田　康平

日本眼科学会総会 2019.4

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Event date： 2019.4

Language：Japanese Presentation type：Oral presentation (general)

Venue：東京都 Country：Japan
糖尿病網膜症における網膜血管閉塞と毛細血管瘤の空間的関連

@海津　嘉弘,@中尾　新太郎,@有馬　充,@和田　伊織,@山口　宗男,@石川　桂二郎,@秋山　雅人,@園田　康平

日本眼科学会総会 2019.4

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Event date： 2019.4

Language：Japanese Presentation type：Oral presentation (general)

Venue：東京都 Country：Japan
低分子化合物投与によるアストロサイトから網膜神経細胞へのリプログラミング

#藤井裕也,@有馬充,@下川翔太郎,@村上祐介,@園田康平

日本再生医療学会総会 2019.3

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Event date： 2019.3

Language：Japanese Presentation type：Symposium, workshop panel (public)

Venue：神戸市 Country：Japan
Novel predictors of treatment-requiring retinopathy of prematurity International conference

@Mitsuru Arima,@Shoko Tsukamoto,@Kohta Fujiwara,@Koh-Hei Sonoda

The 34th congress of asia-pacific academy of ophthalmology 2019.3

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Event date： 2019.3

Language：English Presentation type：Symposium, workshop panel (public)

Venue：Bangkok Country：Thailand
The new development quantification system for the evaluation of disease activity in exudative age-related macular degeneration by using en face hyperreflective foci International conference

#Iori Wada,@Shintaro Nakao,@Yoshihiro Kaizu,@Muneo Yamaguchi,@Mitsuru Arima,@Keijiro Ishikawa,@Kumiko Kano,@Satomi Shiose,@Yuji Oshima,@Tatsuro Ishibashi,@Koh-Hei Sonoda

6TH INTERNATIONAL CONGRESS ON OCT ANGIOGRAPHY AND ADVANCES IN OCT 2018.12

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Event date： 2018.12

Language：English Presentation type：Oral presentation (general)

Venue：Roma Country：Italy
Microaneurysms Imaging in Diabetic Retinopathy using Multiple en face Optical Coherence Tomography Angiography Image Averaging International conference

#Yoshihiro Kaizu,@Shintaro Nakao,@Mitsuru Arima,#Iori Wada,@Keiko Yoshitomi,@Michiko Sugino,@Naoya Hashiguchi,@Kota Hirashima,@Koh-Hei Sonoda

The 11th Joint Meeting of Japan-China-Korea Ophthalmologists 2018.12

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Event date： 2018.12

Language：English Presentation type：Oral presentation (general)

Venue：Fukuoka Country：Japan
The direct reprogramming of retinal astrocytes into neurons with small-molecule compounds International conference

#Yuya Fujii,@Mitsuru Arima,@Shotaro Shimokawa,@Yusuke Murakami,@Koh-Hei Sonoda

The 11th Joint Meeting of Japan-China-Korea Ophthalmologists 2018.12

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Event date： 2018.12

Language：English Presentation type：Oral presentation (general)

Venue：Fukuoka Country：Japan
The evaluation of disease activity in exudative age-related macular degeneration using en face hyperreflective foci International conference

#Iori Wada,@Shintaro Nakao,@Satomi Shiose,#Yoshihiro Kaizu,@Muneo Yamaguchi,@Mitsuru Arima,@Keijiro Ishikawa,@Kumiko Kano,@Yuji Oshima,@Tatsuro Ishibashi,@Sonoda Koh-Hei

The 11th Join Meeting of Japan-China-Korea Ophthalmologists 2018.12

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Event date： 2018.12

Language：English Presentation type：Oral presentation (general)

Venue：Fukuoka Country：Japan
Two case reports of Loeys-Dietz syndrome with retinal vascular abnormality similar to familial exudative vitreoretinopathy International conference

@Shinzo Sakisaka,@Shoko Tsukamoto,@Mitsuru Arima,@Riichiro Kono,@Shigeo Yoshida,@Koh-Hei Sonoda

The 11th Joint Meeting of Japan-China-Korea Ophthalmologists 2018.12

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Event date： 2018.12

Language：English Presentation type：Oral presentation (general)

Venue：Fukuoka Country：Japan
家族性滲出性硝子体網膜症様所見を合併したLoeys-Dietz症候群の2例

@向坂親蔵,@塚本晶子,@有馬充,@向野利一郎,@吉田茂生,@園田康平

日本臨床眼科学会 2018.10

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Event date： 2018.10

Language：Japanese Presentation type：Oral presentation (general)

Venue：東京都 Country：Japan
小児網膜疾患に続発した急性閉塞隅角緑内障に対して周辺部虹彩切除術が有効であった2例

@石龍悠,@村上祐介,@有馬充,@塚本晶子,@池田康博,@園田康平

日本緑内障学会 2018.9

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Event date： 2018.9

Language：Japanese Presentation type：Oral presentation (general)

Venue：新潟市 Country：Japan
AMDの活動性マーカーとしての En Face OCTによるhyperreflective foci

#和田伊織,@中尾新太郎,@大島裕司,@海津嘉弘,@山口宗男,@有馬　充,@石川桂二郎,@狩野久美子,@塩瀬聡美,@石橋達朗,@園田康平

日本眼循環学会 2018.7

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Event date： 2018.7

Language：Japanese Presentation type：Oral presentation (general)

Venue：松本市 Country：Japan
糖尿病網膜症におけるOCT angiographyの網膜血管描出再現性は病期により異なる

#海津嘉弘,@中尾新太郎,@有馬充,#和田伊織,@石川桂二郎,@杉野迪子,@橋口直哉,@吉富景子,@平島昂太,@園田康平

日本眼循環学会 2018.7

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Event date： 2018.7

Language：Japanese Presentation type：Oral presentation (general)

Venue：松本市 Country：Japan
Impact of a ROCK inhibitor ripasudil on distribution of claudin-5 in vascular endothelial cells in diabetic retinopathy International conference

@Mitsuru Arima, @Shintaro Nakao, Feng Hao, Muneo Yamaguchi, @Kensuke Shibata, Yoshihiro Kaizu, Iori Wada, Shigeo Yoshida, @Koh-Hei Sonoda

The Association for Research in Vision and Ophthalmology 2018.5

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Event date： 2018.5

Language：English

Country：Japan
糖尿病黄斑浮腫におけるcluadin-5発現調節へのROCK阻害剤リパスジルの効果

@有馬充, @中尾新太郎, 馮浩, 山口宗男, 海津嘉弘, 和田伊織, 吉田茂生, @園田康平

日本眼科学会総会 2018.4

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Event date： 2018.5

Language：Japanese

Country：Japan
LCC and CPAP are useful predictors of the development of TR-ROP

@Mitsuru Arima, @Shoko Tsukamoto, Kohta Fujiwara, Kanako Yamana, Miwa Murayama, @Koh-Hei Sonoda

Annual Meeting of the Japanese Association of Pediatric Ophthalmology 2018.3

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Event date： 2018.5

Language：English

Country：Japan
小瞳孔を伴うPierson症候群に対して瞳孔形成術を施行した症例

秋山瑠美, @塚本晶子, @有馬充, 村山美和, 向野利一郎, 林田陽, 園田康平

日本小児眼科学会 2018.3

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Event date： 2018.5

Language：Japanese

Country：Japan
Ophthalmic findings of a male infant with Pierson syndrome

Rumi Akiyama, @Shoko Tsukamoto, @Mitsuru Arima, Miwa Murayama, Koh-Hei Sonoda

The 10th Joint Meeting of Korea-China-Japan Ophthalmologists 2017.11

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Event date： 2018.5

Language：English

Country：Japan
ROCK阻害剤を用いた加齢黄斑変性の長期治療に伴う線維化の予防

和田伊織, @中尾新太郎, 山口宗男, @石川桂二郎, 吉田茂生, @有馬充, 磯部友之, 金児佳生, @石橋達朗, @園田康平

日本血管生物医学会 2017.12

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Event date： 2018.5

Language：Japanese

Country：Japan
OCTAによる網膜灌流密度は糖尿病網膜症の無灌流領域検出に有用である

石龍悠, @中尾新太郎, 海津嘉弘, 吉田茂生, @有馬充, 和田伊織, 山口宗男, @石橋達朗, @園田康平

日本眼循環学会 2017.7

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Event date： 2018.5

Language：Japanese

Country：Japan
OCTAによる網膜灌流密度の空間的パターンは糖尿病網膜症の検出に有用である

海津嘉弘, @中尾新太郎, 吉田茂生, @有馬充, 藤原康太, 和田伊織, 山口宗男, @岸本淳司, @石橋達朗, @園田康平

日本眼循環学会 2017.7

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Event date： 2018.5

Language：Japanese

Country：Japan
糖尿病網膜症の網膜血管における claudin-5 発現調節機構

@有馬充, @園田康平

日本眼循環学会 2017.7

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Event date： 2018.5

Language：Japanese

Country：Japan
中枢神経ループスに合併し，両眼性に閉塞性網膜血管症を発症したSLE網膜症の1例

武田篤信, @石川桂二郎, @有馬充, @久冨智朗, 末廣久美子, 疋田伸一, 森　俊輔, 仙石昭仁, 宮村　知也, @園田康平

2017.7

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Event date： 2018.5

Language：Japanese

Country：Japan
Vascular Normalization by ROCK Inhibitor: Therapeutic Potential of Ripasudil (K-115) Eye Drop in Retinal Angiogenesis and Hypoxia

Muneo Yamaguchi, @Shintaro Nakao, Ryoichi Arita, Yoshihiro Kaizu, @Mitsuru Arima, Zhou Yedi, Takeshi Kita, Shigeo Yoshida, Kazuhiro Kimura, Isobe T, Kaneko Y, @Tatsuro Ishibashi, @Koh-Hei Sonoda

The 9th Joint Meeting of Chinese-Japanese-Korean Ophthalmologists 2016.9

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Event date： 2018.5

Language：English

Country：China
Claudin-5 Redistribution Induced by Inflammation Leads to Anti-VEGF Resistant Diabetic Macular Edema Invited

Mitsuru Arima

第26回日本糖尿病眼学会総会. 2020.12
低分子化合物によるMüller細胞からRhodopsin様細胞への形質転換機構の解析

久井貴博, 下川桜子, 山本夏帆, 陶妍, 趙寰宇, 藤井裕也, 有馬充, 村上祐介, 園田康平

日本眼科学会総会 2026.4
低分子化合物による内在性網膜ミュラー細胞の視細胞へのリプログラミング

藤井裕也, 有馬充, 下川翔太郎, 和田伊織, 村上祐介, 園田康平

日本再生医療学会総会 2022.3
TNFRSF10A発現低下はPKC経路を介して網膜色素上皮細胞死を促進する

森賢一郎, 石川桂二郎, 和田伊織, 久保夕樹, 中間崇仁, 秋山雅人, 有馬充, 納富昭司, 村上祐介, 中尾新太郎, 久冨智朗, 吉田茂生, 園田康平

日本眼科学会総会 2021.4
糖尿病網膜症における毛細血管瘤の疎密と臨床的意義の関連性

中尾新太郎, 海津嘉弘, 和田伊織, 有馬充, 山口宗男, 石川桂二郎, 園田康平

日本糖尿病眼学会 2020.10
ボリューメトリック3次元OCT angiographyを用いた増殖糖尿病網膜症における網膜新生血管評価

福田洋輔, 中尾新太郎, 海津嘉弘, 和田伊織, 有馬充, 石川桂二郎, 園田康平

日本糖尿病眼学会 2020.10
小児緑内障を伴ったEmanuel症候群の1例

岡本美里, 有馬充, 村上祐介, 森雄二郎, 関瑛子, 中間崇仁, 下川桜子, 塚本晶子, 園田康平

日本臨床眼科学会 2020.10
Study protocol for natural history and related inflammation in retinitis pigmentosa: RP-PRIMARY Study International conference

Murakami Y, Shimokawa S, Fukushima M, Hirose A, Shimokawa S, Fujiwara K, Tsukamoto S, Hirata A, Takada A, Tokunaga S, Kobayakawa Y, Arima M, Kaida T, Miyata K, Mawatari G, Ishizu M, Ikeda Y, Sonoda KH

ARVO 2023.4
Study protocol for natural history and related inflammation in retinitis pigmentosa: RP-PRIMARY study

Murakami Y, Shimokawa S, Fukushima M, Hirose A, Shimokawa S, Fujiwara K, Tsukamoto S, Hirata A, Takada A, Tokunaga S, Kobayakawa Y, Arima M, Kaida T, Miyata K, Mawatari G, Ishizu M, Ikeda Y, Sonoda KH

The 127th Annual Meeting of the Japanese Ophthalmological Society 2023.4
Direct reprogramming of Müller cells into photoreceptor cells in mice by stimulation with small molecule compounds International conference

Fujii Y, Arima M, Murakami Y, Sonoda KH

ARVO 2022.5

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Venue：Denver Country：United States
Age-related morphologic abnormalities of retinal pigment epithelium in Tnfrsf10 knockout mice International conference

Mori K, Ishikawa K, Wada I, Kubo Y, Nakama T, Akiyama M, Arima M, Murakami Y, Nakao S, Yoshida S, Sonoda KH

The 14th Joint Meeting of Japan-China-Korea Ophthalmologists 2021.11
Downregulation of TNFRSF10A promotes RPE cell death via PKC deactivation International conference

Mori K, Ishikawa K, Wada I, Kubo Y, Nakama T, Akiyama M, Arima M, Notomi S, Murakami Y, Hisatomi T, Nakao S, Yoshida S, Sonoda KH

ARVO 2021.5

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Venue：San Francisco Country：United States
網膜色素変性症に対するスタチン封入ナノ粒子薬の臨床前用量設定研究(Preclinical dose setting study of statin-filled nano-medicine for retinitis pigmentosa)

Fukushima Masatoshi, Shimokawa Sakurako, Tao Yan, Zhao Huanyu, Shimokawa Shotaro, Funatsu Jun, Fujiwara Kohta, Arima Mitsuru, Harada Yuka, Murakami Yusuke, Sonoda Koh-hei

眼科臨床紀要 2024.9 眼科臨床紀要会

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網膜色素変性の自然経過と炎症性指標の関連　PR-PRIMARY研究プロトコル

村上祐介, 下川桜子, 福嶋正俊, 廣瀬文音, 下川翔太郎, 藤原慶太, 塚本晶子, 平田明恵, 高田敦史, 徳永章二, 小早川優子, 有馬充, 貝田智子, 宮田和典, 馬渡剛, 石津正崇, 池田康博, 園田康平

日本眼科学会雑誌 2023.3 (公財)日本眼科学会

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糖尿病網膜症における毛細血管瘤の疎密と血管病変との関連性

中尾新太郎, 和田伊織, 有馬充, 山口宗男, 石川桂二郎, 園田康平

日本糖尿病眼学会誌 2022.8 日本糖尿病眼学会

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ボリューメトリック3次元OCT angiographyを用いたPDRにおける網膜新生血管評価

福田洋輔, 中尾新太郎, 海津嘉弘, 和田伊織, 有馬充, 石川桂二郎, 園田康平

日本糖尿病眼学会誌 2022.8 日本糖尿病眼学会

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「新生児領域における医薬品開発と国際標準化に向けて」　新生児医療における医師主導治験の経験

有馬充

日本新生児成育医学会雑誌 2023.10 (公社)日本新生児成育医学会

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MISC

「新生児領域における医薬品開発と国際標準化に向けて」新生児医療における医師主導治験の経験 Reviewed

有馬充

日本新生児成育医学会雑誌 35 ( 3 ) 451 - 451 2023.10 （ ISSN:2189-7549 ）

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Authorship：Lead author,　Corresponding author Language：Japanese Publisher：(公社)日本新生児成育医学会

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網膜色素変性の自然経過と炎症性指標の関連 PR-PRIMARY研究プロトコル Reviewed

村上祐介, 下川桜子, 福嶋正俊, 廣瀬文音, 下川翔太郎, 藤原慶太, 塚本晶子, 平田明恵, 高田敦史, 徳永章二, 小早川優子, 有馬充, 貝田智子, 宮田和典, 馬渡剛, 石津正崇, 池田康博, 園田康平

日本眼科学会雑誌 127 ( 臨増 ) 209 - 209 2023.3 （ ISSN:0029-0203 ）

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抗VEGF抵抗性糖尿病黄斑浮腫におけるROCKの関与

有馬充

日本糖尿病眼学会誌 26 22 - 29 2022.8 （ ISSN:1881-753X ）

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糖尿病網膜症における毛細血管瘤の疎密と血管病変との関連性 Reviewed

中尾新太郎, 和田伊織, 有馬充, 山口宗男, 石川桂二郎, 園田康平

日本糖尿病眼学会誌 26 147 - 147 2022.8 （ ISSN:1881-753X ）

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抗VEGF抵抗性糖尿病黄斑浮腫におけるROCKの関与 Reviewed

有馬充

日本糖尿病眼学会誌 26 22 - 29 2022.8 （ ISSN:1881-753X ）

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ボリューメトリック3次元OCT angiographyを用いたPDRにおける網膜新生血管評価 Reviewed

福田洋輔, 中尾新太郎, 海津嘉弘, 和田伊織, 有馬充, 石川桂二郎, 園田康平

日本糖尿病眼学会誌 26 148 - 148 2022.8 （ ISSN:1881-753X ）

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未熟児網膜症研究の進歩　未熟児網膜症患者に対するリパスジル点眼の安全性および有効性検証を目的とした第I/II相多施設共同医師主導治験

有馬充

眼科臨床紀要 15 ( 5 ) 347 - 352 2022.5 （ ISSN:1882-5176 ）

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Language：Japanese Publisher：眼科臨床紀要会

未熟児網膜症(ROP)は早産児網膜に生じる血管増殖性疾患である。ROPは代表的小児失明原因疾患であるが、既存治療の適応は侵襲性や合併症のリスクから重症ROPに限定され、重症化するまで経過観察するしかない。我々は過去に、ROCK(Rho-kinase associated protein kinase)阻害薬であるリパスジルの点眼投与により、ROP動物モデルにおける網膜異常血管新生が抑制されることを示した。点眼は侵襲性が低く、リパスジルには成人緑内障・高眼圧症治療薬としての実績があり、これまで全身性の重篤な有害事象の報告もない。点眼による早期治療介入によりROPを重症化させずに治癒できれば視力予後改善につながると考え、リパスジルの安全性・有効性を検証すべく、令和2年11月より九州大学、産業医科大学、山口大学の3施設で第I/II相医師主導治験を開始した。本稿では治験の概要について説明する。(著者抄録)
未熟児網膜症研究の進歩未熟児網膜症患者に対するリパスジル点眼の安全性および有効性検証を目的とした第I/II相多施設共同医師主導治験 Reviewed

有馬充

眼科臨床紀要 15 ( 5 ) 347 - 352 2022.5 （ ISSN:1882-5176 ）

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Industrial property rights

Patent	Number of applications: 0	Number of registrations: 0
Utility model	Number of applications: 0	Number of registrations: 0
Design	Number of applications: 0	Number of registrations: 0
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Professional Memberships

日本眼科学会
日本小児眼科学会
日本国際臨床医学会
日本新生児成育医学会

Committee Memberships

日本新生児成育医学会薬事委員会 Domestic

2023.1 - 2023.9

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Committee type：Academic society

Research Projects

Acute retinal regenerative medicine with low molecular weight cocktail

Grant number：21H03094 2021.4 - 2024.3

Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

Sonoda Koh-Hei

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Grant type：Scientific research funding

In this study, we identified four small molecule compounds that induce the differentiation of retinal endogenous Muller cells into photoreceptor cells.
1．SB431542: transforming growth factor beta inhibitor 2. LDN193189: osteogenic protein inhibitor 3. CHIR99021: glycogen synthase kinase 3 beta inhibitor 4. DAPT: γ-secretase inhibitor
The discovery of these four small molecule compounds could revolutionize the treatment of retinal diseases. They cause Muller cells to permanently express rhodopsin and fix it in the retina, leading to a significant partial recovery of retinal function in disease models.

CiNii Research
Activity biomarker search for intraocular proliferative tissue at the single cell level

Grant number：20K09829 2020.4 - 2023.3

Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

Nakao Shintaro

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Grant type：Scientific research funding

Three approaches were taken to elucidate the pathogenesis of intraocular proliferative diseases. (1) Forty-four cases of epiretinal membrane removed by vitrectomy were collected for single-cell analysis, but the number of cells was 920 per sample, and sufficient cDNA could not be collected. In this analysis, it is considered that appropriate condition setting is necessary for the samples collected by vitrectomy.(2) In a mouse model of proliferative retinopathy, we found a macrophage fraction involved in ischemia by single-cell analysis. (3) In a proliferative diabetic retinopathy model (over-expression of VEGF), we found local proliferation of vitreous resident macrophages. (4)We analyzed the vascular structure of the proliferative membrane in proliferative diabetic retinopathy using OCT angiography, and found that there are three vascular morphologies and the correlation between disease activity and vascular volume.

CiNii Research
リパスジルを用いた未熟児網膜症に対する新規点眼薬の開発

2020 - 2022

日本医療研究開発機構(AMED)

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Grant type：Contract research
未熟児網膜症に対する点眼治療薬の創製

2020

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Grant type：Donation
ROCK阻害剤を用いた抗VEGF治療抵抗性糖尿病黄斑浮腫に対する新規治療法の開発

Grant number：19K18846 2019 - 2020

Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Early-Career Scientists

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Authorship：Principal investigator Grant type：Scientific research funding
未熟児網膜症の進行予防を目的とした点眼薬の開発

2019

日本医療研究開発機構(AMED)

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Authorship：Principal investigator Grant type：Contract research
公益信託参天製薬創業者記念眼科医学研究基金／眼所見を軸としたﾛｲｽ･ﾃﾞｨｰﾂ症候群に対する新しい診断基準の構築

2019

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Grant type：Donation
ポータブルスリットランプとスマートフォンを用いた非接触式眼底カメラの開発

2018.5 - 2021.3

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Grant type：Other funds from industry-academia collaboration
臨床研究助成／Rhoキナーゼ阻害剤を用いた、未熟児網膜症に対する点眼療法の開発

2018

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Grant type：Donation
ふくおか臨床医学研究賞／Rhoキナーゼ阻害剤を用いた、未熟児網膜症に対する点眼療法の開発

2018

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Grant type：Donation
抗VEGF療法に依存しない糖尿病黄斑浮腫根治療法の開発

Grant number：17K16997 2017 - 2018

Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists(A)or(B)

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Authorship：Principal investigator Grant type：Scientific research funding
加齢黄斑変性(AMD)患者のアンメットニーズに応える新たな抗線維化治療

Grant number：19K09931

塩瀬聡美, 石川桂二郎, 園田康平, 秋山雅人, 久冨智朗, 有馬充

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Grant type：Scientific research funding

加齢黄斑変性(AMD)の治療は、脈絡膜新生血管（CNV)に対する治療が中心で、治療後生じる網膜下線維化に有効な治療はない。最終的に網膜下線維化による視機能障害がおこるため、この線維化への対策が不可欠である。線維化に関する様々な蛋白をターゲットとした治療が試みられているが、未だ実用化されていない。我々は、新たなターゲットとしてagrinという蛋白に着目し、網膜下線維巣に有意にagrinが発現していることを、マウスレーザー誘導性CNVモデルにより証明した。網膜下線維化のメカニズムを明らかにし、agrin を標的とした新たな治療を確立することは、AMD 患者のアンメットニーズに応える治療戦略となる。

CiNii Research

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Specialized clinical area

Biology / Medicine, Dentistry and Pharmacy / Surgical Clinical Medicine / Ophthalmology
Other

Year of medical license acquisition

2007