Rho-Kinase/ROCK as a Potential Drug Target for Vitreoretinal Diseases

Abstract

Rho-associated kinase (Rho-kinase/ROCK) was originally identified as an effector protein of the G protein Rho. Its involvement in various diseases, particularly cancer and cardiovascular disease, has been elucidated, and ROCK inhibitors have already been applied clinically for cerebral vasospasm and glaucoma. Vitreoretinal diseases including diabetic retinopathy, age-related macular degeneration, and proliferative vitreoretinoapthy are still a major cause of blindness. While anti-VEGF therapy has recently been widely used for vitreoretinal disorders due to its efficacy, attention has been drawn to new unmet needs. The importance of ROCK in pathological vitreoretinal conditions has also been elucidated and is attracting attention as a potential therapeutic target. ROCK is involved in angiogenesis and hyperpermeability and also in the pathogenesis of various pathologies such as inflammation and fibrosis. It has been expected that ROCK inhibitors will become new molecular target drugs for vitreoretinal diseases. This review summarizes the recent progress on the mechanisms of action of ROCK and their applications in disease treatment.

Figure 1

ROCK-activated vitreoretinal diseases. ROCK activation is involved in the pathology of retinal vitreous diseases such as diabetic retinopathy, age-related macular degeneration, and PVR, termed as “ROCK-activated diseases.” In each disease, the Rho-ROCK signaling pathway is activated by various cytokines, implicating ROCK in various pathology. Therefore, ROCK is a potential therapeutic target for these vitreoretinal diseases.