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Potential Role of Rho-Associated Protein Kinase Inhibitor Y-27632 in Glaucoma Filtration Surgery

¹From the Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan; the ²Department of Ophthalmology and Visual Science, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan; the ³Department of Ophthalmology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

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 -smooth muscle actin (-SMA) expression were examined via immunohistochemistry. In vivo studies in Japanese white rabbits consisted of a full-thickness sclerostomy followed in the 7-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 -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.

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