Kita Takeshi
Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Nippon Ganka Gakkai Zasshi. 2010 Nov;114(11):927-34.
Cicatricial contraction of preretinal fibrous membrane is a cause of severe vision loss in proliferative vitreoretinal diseases such as proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR). In this study, vitreous samples from PDR or PVR patients caused significantly stronger contraction of hyalocyte-containing collagen gels, an in vitro model of cicatricial contraction, compared with those from nonproliferative controls. We elucidated the critical role of transforming growth factor-beta (TGF-beta) in the contractile effect and its underlying mechanisms mediating cicatricial contraction in proliferative vitreoretinal diseases at least in part. Fasudil, a potent and selective Rho-kinase (ROCK) inhibitor, almost completely blocked collagen gel contraction induced by vitreous samples. In addition, fasudil significantly inhibited the progression of experimental PVR in rabbit eyes in vivo. Rho/ROCK pathway, considered to be a key downstream mediator of TGF-beta and other contractile-inducing factors, might become a unique therapeutic target for the treatment of proliferative vitreoretinal diseases.
视网膜前纤维膜的瘢痕收缩是增殖性玻璃体视网膜疾病（如增殖性糖尿病视网膜病变（PDR）和增殖性玻璃体视网膜病变（PVR））导致严重视力丧失的原因之一。在本研究中，与非增殖性对照患者的玻璃体样本相比，PDR或PVR患者的玻璃体样本对含玻璃体细胞的胶原凝胶（瘢痕收缩的体外模型）的收缩作用明显更强。我们至少部分阐明了转化生长因子-β（TGF-β）在增殖性玻璃体视网膜疾病的收缩效应及其介导瘢痕收缩的潜在机制中的关键作用。法舒地尔是一种强效且选择性的Rho激酶（ROCK）抑制剂，几乎完全阻断了玻璃体样本诱导的胶原凝胶收缩。此外，法舒地尔在体内显著抑制了兔眼实验性PVR的进展。Rho/ROCK途径被认为是TGF-β和其他诱导收缩因子的关键下游介质，可能成为治疗增殖性玻璃体视网膜疾病的独特治疗靶点。
