title: Effects of K-115 (Ripasudil), a novel ROCK inhibitor, on trabecular meshwork and Schlemm's canal endothelial cells.
abstract: Ripasudil hydrochloride hydrate (K-115), a specific Rho-associated coiled-coil containing protein kinase (ROCK) inhibitor, was the first ophthalmic solution developed for the treatment of glaucoma and ocular hypertension in Japan. Topical administration of K-115 decreased intraocular pressure (IOP) and increased outflow facility in rabbits. This study evaluated the effect of K-115 on monkey trabecular meshwork (TM) cells and Schlemm's canal endothelial (SCE) cells. K-115 induced retraction and rounding of cell bodies as well as disruption of actin bundles in TM cells. In SCE-cell monolayer permeability studies, K-115 significantly decreased transendothelial electrical resistance (TEER) and increased the transendothelial flux of FITC-dextran. Further, K-115 disrupted cellular localization of ZO-1 expression in SCE-cell monolayers. These results indicate that K-115 decreases IOP by increasing outflow facility in association with the modulation of TM cell behavior and SCE cell permeability in association with disruption of tight junction.
authors.affiliation: Tokyo New Drug Research Laboratories, Kowa Co., Ltd., Tokyo, 189-0022, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kaneko
authors.affiliation: Tokyo New Drug Research Laboratories, Kowa Co., Ltd., Tokyo, 189-0022, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ohta
authors.affiliation: Department of Ophthalmology, Faculty of Life Sciences, Kumamoto University, Kumamoto, 860-8556, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Tokyo New Drug Research Laboratories, Kowa Co., Ltd., Tokyo, 189-0022, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Mizuno
authors.affiliation: Tokyo New Drug Research Laboratories, Kowa Co., Ltd., Tokyo, 189-0022, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Isobe
authors.affiliation: Tokyo New Drug Research Laboratories, Kowa Co., Ltd., Tokyo, 189-0022, Japan.
authors.forename: Sohei
authors.initials: S
authors.lastname: Tanabe
authors.affiliation: Department of Ophthalmology, Faculty of Life Sciences, Kumamoto University, Kumamoto, 860-8556, Japan.
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Tanihara
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005901:Glaucoma / Q000188:drug therapy / Q000378:metabolism; D000882:Haplorhini; D007429:Intraocular Pressure / Q000187:drug effects; D007546:Isoquinolines / Q000494:pharmacology*; D007564:Japan; D008297:Male; D009798:Ocular Hypertension / Q000188:drug therapy / Q000378:metabolism; D009883:Ophthalmic Solutions / Q000494:pharmacology; D011817:Rabbits; D013449:Sulfonamides / Q000494:pharmacology*; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism; D014129:Trabecular Meshwork / Q000187:drug effects* / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000378:metabolism; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000199:Actins; D007546:Isoquinolines; C584679:K-115; D009883:Ophthalmic Solutions; D013449:Sulfonamides; D062826:Zonula Occludens-1 Protein; D054460:rho-Associated Kinases