title: The new therapeutic concept of using a rho kinase inhibitor for the treatment of corneal endothelial dysfunction.
abstract: 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.
authors.affiliation: Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Okumura
authors.forename: Noriko
authors.initials: N
authors.lastname: Koizumi
authors.forename: Morio
authors.initials: M
authors.lastname: Ueno
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sakamoto
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Junji
authors.initials: J
authors.lastname: Hamuro
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kinoshita
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003316:Corneal Diseases / Q000188:drug therapy*; D004728:Endothelium, Corneal / Q000187:drug effects* / Q000293:injuries; D008252:Macaca fascicularis; D023421:Models, Animal; D009883:Ophthalmic Solutions / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D014945:Wound Healing / Q000187:drug effects; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
chemical_list: D009883:Ophthalmic Solutions; D047428:Protein Kinase Inhibitors; D054460:rho-Associated Kinases