Therapeutic Potential and Mechanisms of Rock Inhibition on the Progression of Proliferative Vitreoretinal Diseases

Abstract

Purpose: : We previously reported that Rho-kinase (ROCK) inhibitor has a therapeutic potential on cicatricial contraction of preretinal proliferative membrane, which directly causes severe vision loss, in proliferative vitreoretinal diseases such as proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR). In this study, we investigated its cellular mechanisms.

Methods: : Bovine hyalocytes were embedded in type I collagen gels and stimulated with recombinant transforming growth factor-β2 (TGF-β2) or human vitreous samples which were collected from patients with PDR or PVR in the presence or absence of fasudil, a potent and selective ROCK inhibitor. In addition, the expression and organization of -smooth muscle actin (-SMA) in hyalocytes were examined by western blotting and immunocytochemical analysis, respectively. In vivo, the effects of fasudil on the progression of experimental PVR in rabbit eyes were also investigated. Fasudil was injected into the vitreous cavity from stage 0 PVR in which proliferative membrane has not been formed yet, or from stage 2 PVR in which the membrane has already been formed.

Results: : Recombinant TGF-β2 and vitreous samples with proliferative diseases promoted hyalocyte-containing collagen gel contraction with enhanced -SMA expression by hyalocytes. Fasudil disrupted the organization of -SMA, but didn’t affect its expression. In vivo, intravitreal injection of fasudil suppressed the progression of experimental PVR both from stage 0 and from stage 2. In addition, fasudil also disrupted the organization of -SMA in the proliferative membranes in experimental PVR without affecting its expression.

Keywords: diabetic retinopathy • proliferative vitreoretinopathy • vitreous