title: [Molecular mechanisms of preretinal membrane contraction in proliferative vitreoretinal diseases and ROCK as a therapeutic target].
abstract: 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.
authors.affiliation: Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. kita@eye.med.kyushu-u.ac.jp
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kita
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D003930:Diabetic Retinopathy / Q000188:drug therapy / Q000503:physiopathology; D058990:Molecular Targeted Therapy; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011817:Rabbits; D018630:Vitreoretinopathy, Proliferative / Q000188:drug therapy* / Q000503:physiopathology*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
chemical_list: D047428:Protein Kinase Inhibitors; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054460:rho-Associated Kinases; C049347:fasudil