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Abstract #66557 Published in IGR 17-3

Effects of K-115 (Ripasudil), a novel ROCK inhibitor, on trabecular meshwork and Schlemm's canal endothelial cells

Kaneko Y; Ohta M; Inoue T; Mizuno K; Isobe T; Tanabe S; Tanihara H
Scientific reports 2016; 6: 19640

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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.

Tokyo New Drug Research Laboratories, Kowa Co., Ltd., Tokyo, 189-0022, Japan.

Full article

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Classification:

11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
2.5.1 Trabecular meshwork (Part of: 2 Anatomical structures in glaucoma > 2.5 Meshwork)
2.5.2 Schlemms canal (Part of: 2 Anatomical structures in glaucoma > 2.5 Meshwork)
3.6 Cellular biology (Part of: 3 Laboratory methods)

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