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The New Therapeutic Concept of Using a Rho Kinase Inhibitor for the Treatment of Corneal Endothelial Dysfunction

Okumura, Naoki MD, PhD; Koizumi, Noriko MD, PhD; Ueno, Morio MD, PhD; Sakamoto, Yuji; Takahashi, Hiroaki BSc; Hamuro, Junji PhD; Kinoshita, Shigeru MD, PhD

doi: 10.1097/ICO.0b013e3182281ee1

Corneal endothelial cells (CECs) show poor regenerative ability in humans, and noncompensatory damage of CECs causes irreversible corneal haziness in cases of bullous keratopathy. Although corneal transplantations provide considerable clinical benefits, allograft rejection, primary graft failure, and the shortage of donor corneas are problems that still need to be overcome. The establishment of new treatment therapies is the key to solving these problems, and we have attempted to establish a new clinical intervention for corneal endothelial dysfunction. We previously demonstrated that the inhibition of Rho/Rho kinase (ROCK) signaling by Y-27632, a specific ROCK inhibitor, promoted cell adhesion, inhibited apoptosis, and enhanced cell proliferation in cultured primate CECs. These results raise the possibility that the ROCK inhibitor might serve as a new tool for establishing an effective culture method for newly emerging cultivated CEC transplantation therapies. Moreover, because Y-27632 enhances cell proliferation in vitro, we hypothesized that the use of a ROCK inhibitor could be a new pharmacological intervention for the treatment of corneal endothelial dysfunction. We demonstrated that the topical instillation of a ROCK inhibitor promotes corneal endothelium wound healing in an animal model. This indicates that use of a ROCK inhibitor is a less invasive and novel therapy that should prove promising for the treatment of corneal endothelial dysfunction.

From the *Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan; and †Department of Biomedical Engineering, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Japan.

Supported in part by the Adaptable and Seamless Technology Transfer Program through Target-driven R&D (AS2111180G to N.K. and S.K.) from the Japan Science and Technology Agency and the Funding Program for Next Generation World-Leading Researchers from the Cabinet Office in Japan (LS117 to N.K.).

The authors state that they have no financial or conflicts of interest to disclose.

Reprints: Noriko Koizumi, Department of Biomedical Engineering, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe 610-0321, Japan (e-mail:

Copyright © 2011 Wolters Kluwer Health, Inc. All rights reserved.