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 downstream target of a small GTPase, Rho. The kinase has been reported to regulate actomyosin-based contractility of smooth muscles by modulation of myosin phosphatase activity. Contractility of ciliary muscle could be implicated in regulation of intraocular pressure while that of ocular vessels could affect blood flow to retina. The present study has been performed to investigate the effect of a ROCK inhibitor on intraocular pressure in rabbits.

METHODS

An inhibitor of ROCK, Y-27632, was dissolved in an ophthalmic solution and topically administered to the eye of a Japanese white rabbit. Intraocular pressure was measured by pneumatonography (n = 12, 24 eyes). Constriction of ciliary muscle was measured by the Magnus method using 12 eyes.

RESULTS

Topical application of 0.1 and 0.03% Y-27632 significantly decreased the intraocular pressure, with maximum decreases of 5.3 and 4.3 mm Hg after 90 minutes compared with the control eye. Y-27632 inhibited the carbachol-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 which was previously constricted by carbachol suggesting that the inhibitor acts to increase the uveoscleral outflow. Our results suggest that the ROCK inhibitor is a promising treatment for glaucoma therapy in the next generation.