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Tomoki Shimada, Naoki Okumura, Ryota Inoue, Yugo Okazaki, Shinichiro Nakano, Shigeru Kinoshita, Noriko Koizumi; Effect of the rho-associated kinase inhibitor eye drop ripasudil on corneal endothelial wound healing in a rabbit corneal endothelial damage model. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5293.
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© ARVO (1962-2015); The Authors (2016-present)
We reported that rho-associated kinase (ROCK)-inhibitor Y-27632 promoted corneal endothelial cell (CEC) proliferation, and that inhibition of ROCK may be a potent therapeutic target for corneal endothelial diseases. In 2014, GLANATEC® ophthalmic solution 0.4% (Kowa Co.), a ripasudil selective ROCK inhibitor, was approved for treating glaucoma and ocular hypertension in Japan. The purpose of this study was to investigate the feasibility of using ripasudil eye drops to treat corneal endothelium injuries.
We mechanically scraped 50% of the corneal endothelium area in 18 rabbit eyes to create a corneal endothelium damage model. Then, 0.4% ripasudil eye drops were instilled 3 times a day in 9 eyes, and a vehicle was applied in 9 eyes as a control. To investigate cell proliferation, corneal endothelium was stained by Ki67 after 48 hours (n=3). The anterior segment was evaluated by slit-lamp microscopy and central corneal thickness was measured by ultrasound pachymetry for 14 days (n=6). Cellular morphology, expression of N-cadherin, Na+/K+-ATPase, and Ki67 was examined by immunocytochemistry.
After 48 hours, the control eyes showed 52.6±1.3% of the cell population as Ki67-positive, whereas the ripasudil-treated eyes showed 91.5±2.0% Ki67-positive cells (p<0.01). Five of 6 corneas became transparent in the ripasudil-treated eyes, whereas 0 of 6 corneas became transparent in the control eyes. After 14 days, the mean central corneal thickness of the ripasudil-treated eyes was 392.8±12.8μm, while that of the control eyes was 1200μm (p<0.01). Immunohistochemical analysis showed that the CEC density of the ripasudil-treated eyes was significantly higher in all areas (non-damaged areas, border, and damaged areas) than in the control eyes (p<0.01). Moreover, the ripasudil-treated eyes expressed N-cadherin and Na+/K+-ATPase in almost all CECs, whereas this expression was decreased in the control eyes. Ki67 expression was not observed in either the ripasudil-treated or control eyes after 48 hours.
Our findings show that ripasudil eye drops promoted corneal endothelial wound healing in an animal model, thus suggesting that ripasudil may be a potent pharmaceutical agent for treating acute corneal endothelial damage following any injury, such as invasive cataract surgery or corneal trauma.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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