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Abstract #20065 Published in IGR 9-4
Potential role of rho-associated protein kinase inhibitor y-27632 in glaucoma filtration surgery
Honjo M; Tanihara H; Kameda T; Kawaji T; Yoshimura N; Araie MInvestigative Ophthalmology and Visual Science 2007; 48: 5549-5557
PURPOSE: To investigate the role of Y-27632, a specific inhibitor of Rho-associated protein kinase (ROCK) in regulating human Tenon fibroblast (HTF) activities including proliferation, adhesion, contraction, migratory response, and myofibroblast transdifferentiation. Effects of Y-27632 on prevention of postoperative scar formation were also examined in a rabbit model of glaucoma filtration surgery. METHODS: After treatment of HTFs with Y-27632, cell toxicity, proliferation, migration, adhesion, and contraction were studied. The cytoskeleton and alpha-smooth muscle actin (alpha-SMA) expression were examined via immunohistochemistry. In-vivo studies in Japanese white rabbits consisted of a full-thickness sclerostomy followed in the seven-day postoperative period by topical application of Y-27632. Intraocular pressure, morphologic changes in bleb features, and histology of surgical sites were evaluated. RESULTS: Y-27632 had no direct toxicity or significant effects on cell proliferation of HTF. The cell adhesion assay showed that Y-27632 promoted adhesiveness to both fibronectin and collagen type I. Use of Y-27632 significantly inhibited collagen gel contraction and alpha-SMA expression in HTFs. Y-27632 also increased HTF motility. In vivo, Y-27632 inhibited wound healing and fibroproliferation after filtration surgery and significantly improved surgical outcome compared with the vehicle. Histologic examination revealed that blebs in the Y-27632-treated group differed from those in the vehicle-treated group in that they lacked significant collagen deposition in the sclerostomy area. CONCLUSIONS: Y-27632 had profound effects on activities of HTFs and was effective in preventing fibroproliferation and scar formation in a rabbit model of glaucoma surgery. A ROCK inhibitor may be an effective anti-scarring agent after glaucoma filtering surgery.
Dr. M. Honjo, Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan
Classification:
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
12.8.10 Woundhealing antifibrosis (Part of: 12 Surgical treatment > 12.8 Filtering surgery)
5.3 Other (Part of: 5 Experimental glaucoma; animal models)
