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Abstract #25282 Published in IGR 12-1
The possibility of selective Rho-associated kinase (ROCK) inhibitors as a medical treatment for glaucoma
Honjo MNippon Ganka Gakkai Zasshi 2009; 113: 1071-1081
Some of the cytokines and growth factors in the aqueous humor activate Rho, and the Rho/ROCK signal transduction participates in signaling pathways via rearrangement of actin cytoskeleton that leads to various cellular reactions. In a previous study, we demonstrated that a selective ROCK inhibitor significantly reduced intraocular pressure, the mechanism of which was attributed to improved outflow. ROCK inhibitors induced the actomyosin assembly, cell adhesive interactions, and the expression of extracellular matrix (ECM) proteins in cultured TM cells. The inhibition of Rho also has been implicated in pathological wound healing by regulating neovascularization, migration, and ECM in scar tissue. In this study, we investigated the role of ROCK inhibitor in regulating human Tenon fibroblast (HTF) activity and postoperative scar formation in a rabbit sclerostomy model. ROCK inhibitor showed decreased aSMA expression in HTF, and prevented enhanced contractility, assembly of actin stress fibers, and myofibroblastic transdifferentiation. In vivo sclerostomy studies showed that the bleb survival was significantly improved in ROCK inhibitor-treated eyes. In another study by us, ROCK inhibitor showed neuroprotective effects against rat retinal ischemia reperfusion injury. Collectively, ROCK inhibitors are thus a potential new strategy for developing medical therapy for glaucomatous dis- LA: Japanese
M. Honjo. Department of Ophthalmology, Tokyo Metropolitan Geriatric Hospital, Japan. m_honjo@kuhp.kyoto-u.ac.jp
Classification:
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
