Yamaguchi Muneo, Nakao Shintaro, Arima Mitsuru, Wada Iori, Kaizu Yoshihiro, Hao Feng, Yoshida Shigeo, Sonoda Koh-Hei
Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan.
J Ophthalmol. 2017;2017:8543592. doi: 10.1155/2017/8543592. Epub 2017 May 10.
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.
Rho相关激酶(Rho激酶/ROCK)最初被鉴定为G蛋白Rho的效应蛋白。其在各种疾病,特别是癌症和心血管疾病中的作用已得到阐明,并且ROCK抑制剂已在临床上用于治疗脑血管痉挛和青光眼。包括糖尿病视网膜病变、年龄相关性黄斑变性和增殖性玻璃体视网膜病变在内的玻璃体视网膜疾病仍然是失明的主要原因。虽然抗VEGF治疗因其疗效最近已被广泛用于玻璃体视网膜疾病,但人们也关注到了新的未满足需求。ROCK在病理性玻璃体视网膜疾病中的重要性也已得到阐明,并作为潜在的治疗靶点受到关注。ROCK参与血管生成和高通透性,也参与炎症和纤维化等各种病理过程的发病机制。人们期望ROCK抑制剂将成为玻璃体视网膜疾病的新型分子靶向药物。本综述总结了ROCK作用机制及其在疾病治疗中的应用的最新进展。