Reduction of intraocular pressure by topical administration of an inhibitor of the Rho-associated protein kinase

Purpose. Rho-associated coiled coil-forming protein kinase (ROCK) is a down stream target of a small GTPase, Rho. The kinase has been reported to regul ate actomyosin-based contractility of smooth muscles by modulation of myosi n phosphatase activity. Contractility of ciliary muscle could be implicated in regulation of intraocular pressure while that of ocular vessels could a ffect blood flow to retina. The present study has been performed to investi gate the effect of a ROCK inhibitor on intraocular pressure in rabbits. Methods. An inhibitor of ROCK, Y-27632, was dissolved in an ophthalmic solu tion and topically administered to the eye of a Japanese white rabbit. Intr aocular pressure was measured by pneumatonography (n = 12, 24 eyes). Constr iction of ciliary muscle was measured by the Magnus method using 12 eyes. Results. Topical application of 0.1 and 0.03% Y-27632 significantly decreas ed the intraocular pressure, with maximum decreases of 5.3 and 4.3 mmHg aft er 90 minutes compared with the control eye. Y-27632 inhibited the carbacho l-induced constriction of rabbit ciliary muscle. Conclusions. The ROCK inhibitor reduced intraocular pressure in rabbits by topical instillation. The inhibitor relaxed the excised ciliary muscle whic h was previously constricted by carbachol suggesting that the inhibitor act s to increase the uveoscleral outflow. Our results suggest that the ROCK in hibitor is a promising treatment for glaucoma therapy in the next generatio n.