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Iori Wada, Shintaro Nakao, Keijiro Ishikawa, Muneo Yamaguchi, Yoshihiro Kaizu, Shigeo Yoshida, Koh-hei Sonoda; The ROCK inhibitor ripasudil suppresses angio-fibrotic switch in subretinal fibrovascular proliferation. Invest. Ophthalmol. Vis. Sci. 2018;59(9):65.
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Angio-fibrotic switch is occasionally induced during fibrosis development in neovascular age-related macular degeneration (AMD) after treatment with anti-VEGF compounds. The purpose of this study was to investigate the impact of the Rho-associated coiled coil–containing protein kinase (ROCK) inhibitor, ripasudil, on angio-fibrotic switch in subretinal fibrovasucular proliferation induced by laser injury.
C57BL/6J mice underwent retinal laser photocoagulation to induce CNV-related fibrosis. BSS (control), aflibercept (400 mg/mL), ripasudil (30 μmol/L), or the combination were administered intravitreally every three days from the 14th day after laser injury. The choroidal whole-mounts were immunofluorescently stained using α-SMA and CD31 from the 28th day after laser injury.
Intravitreal treatment with ripasudil, aflibercept (IVA) or the combination of these drugs reduced the volume of the CD31-positive regions. However, intravitreal administration of ripasudil or the combination therapy, but not IVA, reduced the volume of the α-SMA-positive regions (58.4% reduction from baseline with 30 μmol/L ripasudil, p<0.01 vs control; and 53.8% reduction from baseline with combination therapy, p<0.05 vs control). Furthermore, the ratio of the maximum lengths of CD31 vs, α-SMA positive regionswas significantly decreased by IVA, but not by ripasudil or the combination therapy.
Anti-VEGF therapy specifically inhibited the vascular component. Importantly, the novel ROCK inhibitior, ripasudil, may have therapeutic potential in controlling angio-fibrotic switch in subretinal fibrovascular proliferation.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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