Effect of the Rho Kinase Inhibitor Y-27632 on Corneal Endothelial Wound Healing

The purpose of this study was to investigate the feasibility of using Rho-associated kinase (ROCK) inhibitor eye drops for treating severe corneal endothelial damage due to surgical invasion. A rabbit corneal endothelial damage model was created by mechanically scraping half the area of the corneal...

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Bibliographic Details
Published in:Investigative ophthalmology & visual science 2015-09, Vol.56 (10), p.6067-6074
Main Authors: Okumura, Naoki, Inoue, Ryota, Okazaki, Yugo, Nakano, Shinichiro, Nakagawa, Hiroko, Kinoshita, Shigeru, Koizumi, Noriko
Format: Article
Language:English
Subjects:
Amides - pharmacology
Animals
Cell Proliferation
Cells, Cultured
Corneal Injuries - drug therapy
Corneal Injuries - enzymology
Corneal Injuries - pathology
Disease Models, Animal
Endothelium, Corneal - enzymology
Endothelium, Corneal - injuries
Endothelium, Corneal - pathology
Enzyme Inhibitors - pharmacology
Humans
Pilot Projects
Pyridines - pharmacology
Rabbits
rho-Associated Kinases - antagonists & inhibitors
Wound Healing - drug effects
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Summary:The purpose of this study was to investigate the feasibility of using Rho-associated kinase (ROCK) inhibitor eye drops for treating severe corneal endothelial damage due to surgical invasion. A rabbit corneal endothelial damage model was created by mechanically scraping half the area of the corneal endothelium of eighteen eyes of Japanese white rabbits. A selective ROCK inhibitor, Y-27632 (10 mM), was applied topically for 2 weeks, and then the anterior segment was evaluated by slitlamp microscopy. The corneal endothelium was evaluated by phalloidin staining and immunohistochemical analysis. We then conducted pilot clinical research and applied Y-27632 eye drops topically to three patients who exhibited severe corneal edema due to corneal endothelial damage. In the corneal endothelial damage rabbit model, more Ki67-positive cells were detected in Y-27632-treated eyes than in control eyes. Five of six corneas became transparent in Y-27632-treated eyes, whereas zero of six corneas became transparent in the control eyes (P < 0.01). Actin fibers were distributed at the cell cortex in the eyes treated with Y-27632, whereas actin distribution was partially disrupted, and stress fibers were observed in control eyes. N-cadherin and Na+/K+-ATPase were expressed in almost all cells in Y-27632-treated eyes, but expression decreased in control eyes. Preliminary human cases confirmed that ROCK inhibitor eye drops were considerably effective for treatment of corneal edema associated with cataract surgery. ROCK inhibitor may be developed as an eye drop for treating acute corneal endothelial damage to prevent progression of bullous keratopathy. (University Hospital Medical Information Network Clinical Trial Registry no. UMIN000003625; www.umin.ac.jp/ctr).
ISSN:1552-5783
1552-5783
DOI:10.1167/iovs.15-17595