ROCK inhibitor Ripasudil (K-115) suppresses subretinal fibrosis in laser-induced CNV model

Abstract

Purpose : Subretinal fibrosis is known to develop occasionally in neovascular age-related macular degeneration after anti-VEGF therapy. However, there is no appropriate treatment for the fibrosis. The purpose of this study was to investigate the impact of a Rho-associated coiled coil–containing protein kinase (ROCK) inhibitor ripasudil (K-115) on the subretinal fibrosis after choroidal neovascularization.

Methods : C57BL/6J mice underwent laser photocoagulation to induce CNV-related fibrosis. Ripasudil (3 or 30 μmol/L) and fasudil (30 μmol/L) were treated intravitreally every 3 days from the 14th day after laser injury. The volume of fibrosis was quantified with flat mounts stained by type 1 collagen on day 28 after laser injury.

Results : Intravitreal high but not low concentration ripasudil treatment could reduce the volumes of fibrosis significantly (46.6% reduction from baseline at 30 μmol/L ripasudil; p<0.05 vs control and 5.0% reduction from baseline at 3 μmol/L ripasudil; p=0.99 vs control). On the other hand, fasudil could not affect significantly the volumes of fibrosis (26.4% reduction from baseline at 30 μmol/L fasudil; p=0.50 vs control).

Conclusions : Novel ROCK inhibitior ripasudil has the therapeutic potential for the treatment of subretinal fibrosis in neovascular age-related macular degeneration.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.