Effect of the Rho-Associated Kinase Inhibitor Eye Drop (Ripasudil) on Corneal Endothelial Wound Healing.

作者: Naoki Okumura , Yugo Okazaki , Ryota Inoue , Kazuya Kakutani , Shinichiro Nakano

DOI: 10.1167/IOVS.15-18586

关键词:

摘要: PURPOSE Ripasudil (Glanatec), a selective rho-associated coiled coil-containing protein kinase (ROCK) inhibitor, was approved as glaucoma and ocular hypertension treatment in Japan 2014. The purpose of this study to investigate the feasibility using ripasudil eye drops treat corneal endothelial injuries. METHODS Cultured human cells (HCECs) were treated with ripasudil, 5-bromo-2'-deoxyuridine (BrdU) incorporation evaluated by ELISA. A rabbit damage model also created mechanically scraping endothelium, followed topical drop application for 2 weeks. anterior segment slit-lamp microscopy, central thickness measured ultrasound pachymetry. Corneal specimens phalloidin staining immunohistochemical analysis antibodies against Ki67, N-cadherin, Na+/K+-ATPase. RESULTS Many more BrdU-positive observed among HCECs (0.3-30 μM) than control HCECs. Ripasudil-treated eyes showed 91.5 ± 2.0% Ki67-positive after 48 hours, whereas 52.6 1.3%. Five six corneas became transparent ripasudil-treated eyes, zero eyes. Regenerated cell densities higher vehicle. Eyes expressed N-cadherin Na+/K+-ATPase almost all CECs, expression decreased CONCLUSIONS promoted wound healing, supporting its development treating acute due surgeries, especially cataract surgery.

参考文章(44)
Teruo Tanishima, Masao Matsubara, Wound-healing of the corneal endothelium in the monkey: a morphometric study. Japanese Journal of Ophthalmology. ,vol. 26, pp. 264- 273 ,(1982)
V. P. T. Hoppenreijs, E. Pels, W. F. Treffers, G. F. J. M. Vrensen, Effects of platelet-derived growth factor on endothelial wound healing of human corneas. Investigative Ophthalmology & Visual Science. ,vol. 35, pp. 150- 161 ,(1994)
V P Hoppenreijs, J Oosting, W F Treffers, G F Vrensen, E Pels, Effects of human epidermal growth factor on endothelial wound healing of human corneas. Investigative Ophthalmology & Visual Science. ,vol. 33, pp. 1946- 1957 ,(1992)
Donald T.H. Tan, Prathiba Janardhanan, Huijun Zhou, Yiong-Huak Chan, Hla Myint Htoon, Leonard P.K. Ang, Laurence S. Lim, Penetrating keratoplasty in Asian eyes: the Singapore Corneal Transplant Study. Ophthalmology. ,vol. 115, pp. 975- 982 ,(2008) , 10.1016/J.OPHTHA.2007.08.049
Bourne Wm, Clinical estimation of corneal endothelial pump function. Transactions of the American Ophthalmological Society. ,vol. 96, pp. 229- 242 ,(1998)
Teruo Tanishima, Masao Matsubara, Wound-healing of corneal endothelium in monkey: an autoradiographic study. Japanese Journal of Ophthalmology. ,vol. 27, pp. 444- 450 ,(1983)
Shuh Narumiya, Tatsuya Sawamura, Hidenobu Tanihara, Beatrice Y. J. T. Yue, Yoshihito Honda, Megumi Honjo, Noriaki Kido, Masaru Inatani, Effects of Rho-Associated Protein Kinase Inhibitor Y-27632 on Intraocular Pressure and Outflow Facility Investigative Ophthalmology & Visual Science. ,vol. 42, pp. 137- 144 ,(2001)
Joris Langedijk, Aukje K. Mantel-Teeuwisse, Diederick S. Slijkerman, Marie-Hélène D.B. Schutjens, Drug repositioning and repurposing: terminology and definitions in literature Drug Discovery Today. ,vol. 20, pp. 1027- 1034 ,(2015) , 10.1016/J.DRUDIS.2015.05.001
Karly P. Garnock-Jones, Ripasudil: First Global Approval Drugs. ,vol. 74, pp. 2211- 2215 ,(2014) , 10.1007/S40265-014-0333-2
Hideki Tokushige, Masaru Inatani, Shingo Nemoto, Hideyuki Sakaki, Koushirou Katayama, Masayoshi Uehata, Hidenobu Tanihara, Effects of topical administration of y-39983, a selective rho-associated protein kinase inhibitor, on ocular tissues in rabbits and monkeys. Investigative Ophthalmology & Visual Science. ,vol. 48, pp. 3216- 3222 ,(2007) , 10.1167/IOVS.05-1617