Therapeutic potential of topical ROCK inhibitor Ripasudil (K-115) in choroidal neovascularization

摘要

Purpose : Anti-VEGF therapy is widely used for age related macular degeneration in clinic. However, frequent intravitreal injections are needed for maximum effect. In this study, we investigated the therapeutic potential of a topical Rho-associated protein kinase (ROCK) inhibitor, ripasudil (K-115), in pathological choroidal neovascularization (CNV). Methods : C57BL/6J mice underwent retinal laser photocoagulation to induce CNV. Experiment 1. Ripasudil (3 or 30 ?μmol/L) as well as aflibercept were treated intravitreally every 3 days after laser injury. Experiment 2. A physiological saline solution, a 0.4% ripasudil ophthalmic solution, or a 0.8% ripasudil ophthalmic solution was applied topically to both eyes of the animals 3 times daily for 7 days. The volume of CNV was quantified with choroidal flat mounts stained by lectin. Results : 1. Intravitreal ripasudil treatment could reduce the volumes of CNV significantly at the similar level of aflibercept treatment (49% reduction from baseline at 3 ?μmol/L ripasudil; p0.01 vs control, 56% reduction at 30 ?μmol/L ripasudil; p0.01 vs control). 2. The volumes of CNV at day 7 after laser injury was significantly reduced in a 0.8% ripasudil ophthalmic solution groups (32% reduction from baseline at 0.4% ripasudil; p=0.06 vs saline, 41% reduction at 0.8% K-115; p=0.03 vs saline). Conclusions : Topical as well as intravitreal ripasudil treatment has the potential to become a novel therapeutic strategy in the treatment of choroidal neovascularization. This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.