Effects of ripasudil, a ROCK inhibitor, on retinal edema and nonperfusion area in a retinal vein occlusion murine model

Rho-associated coiled-coil containing protein kinase (ROCK) inhibitors are used to treat glaucoma patients and have protective effects on ischemic states. However, it is poorly understood how the ROCK pathway affects the pathological signs of retinal vein occlusion (RVO). In this study, we evaluated the effects of ripasudil, a ROCK inhibitor, on a murine RVO model. In vivo, RVO was induced by retinal vein laser irradiation in mice, and evaluated with ripasudil. In vitro, the effects of ripasudil were examined on tight junction protein integrity in human retinal microvascular endothelial cells (HRMECs). Moreover, we investigated the expression level of the phosphorylated myosin phosphatase target protein (MYPT)-1 after administration of ripasudil. Ripasudil significantly prevented deterioration, such as retinal edema, reduced the size of the nonperfusion area, and improved retinal blood flow. Ripasudil treatment inhibited disintegration of ZO-1 in HRMECs. Administration of ripasudil suppressed retinal phosphorylation of MYPT-1 in a murine RVO model. These findings indicate that ripasudil might be as a possible therapeutic agent for RVO. (c) 2018 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.