Development of therapeutic strategy targeting EMT against intraocular fibrosis
Project/Area Number |
17H05101
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Research Category |
Grant-in-Aid for Young Scientists (A)
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Allocation Type | Single-year Grants |
Research Field |
Ophthalmology
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Research Institution | Kyushu University |
Principal Investigator |
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥21,320,000 (Direct Cost: ¥16,400,000、Indirect Cost: ¥4,920,000)
Fiscal Year 2019: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2018: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Fiscal Year 2017: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
|
Keywords | 線維化 / 上皮間葉転換 / 形質転換 / マトリセルラー蛋白 / 網膜 / 加齢黄斑変性 / 増殖硝子体網膜症 / 眼科学 / トランスレーショナルリサーチ / 糖尿病網膜症 / 上皮間葉移行 |
Outline of Final Research Achievements |
To develop novel therapy against intra-ocular fibrosis, we first tested the effect of several chemical compounds and found ROCK inhibitors as promising drug that enables significant suppression of RPE (retinal pigment epithelium)-EMT (epithelial-to-mesenchymal transition). We evaluated the drug’s stability in the eye after vitreous injection. In vivo experiment using animal model of intra-ocular fibrosis revealed the drug’s efficacy inhibiting fibrosis development. We further investigate the ROCK inhibitor’s potential for successful RPE cell transplantation therapy. To investigate periostin (PN) and tenascin-C (TNC) expression in the aqueous humor and trabeculectomy specimens of patients with neovascular glaucoma (NVG) secondary to proliferative diabetic retinopathy (PDR). The NVG group had significantly higher levels of PN and TNC compared with the PDR group. Increased PN and TNC expression suggests their possible involvement in the pathogenesis of NVG secondary to PDR.
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Academic Significance and Societal Importance of the Research Achievements |
ROCK阻害剤の眼内線維増殖に対する薬効、薬理学的解析がなされ、将来的に臨床応用されれば、患者の視機能維持が期待され、その社会貢献ははかり知れない。また、新規治療により硝子体手術や抗VEGF薬硝子体注射件数を減少させることができる可能性があり、患者負担の軽減だけでなく、医療財政の観点からも有益となる。
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Report
(4 results)
Research Products
(11 results)
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[Presentation] An association between RPE disruption and fibrotic scar formation after aflibercept therapy for neovascular age-related macular degeneration2019
Author(s)
Ishikawa K, Shiose S, Akiyama M, Kano K, Kaizu Y, Wada I, Nakao S, Oshima Y, Sonoda KH
Organizer
ARVO, Vancouver, Canada
Related Report
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[Presentation] ROCK inhibitor Ripasudil (K-115) suppresses subretinal fibrosis in laser-induced CNV model2017
Author(s)
Wada I, Nakao S, Yamaguchi M, Ishikawa K, Yoshida S, Kaizu Y, Isobe T, Kaneko Y, Ishibashi T, Sonoda KH
Organizer
ARVO, Baltimore, USA, 2017
Related Report
Int'l Joint Research