Rho-associated coiled coil-forming protein kinase (ROCK) is thought to
regulate actomyosin-based contractility in many types of cells. Contractility
of ciliary muscle (CM) and/or trabecular meshwork (TM) could be implicated in
regulation of intraocular pressure, failure of which is a possible cause of
glaucoma. We investigated the effect of inhibitors of ROCK, Y-27632 and
Y-39983, on intraocular pressure (IOP) and contractility of CM and TM.
METHODS. The ROCK inhibitor was topically administered to the eye of a
Japanese white rabbit. IOP was measured by pneumatonography. Measurements of
isometric tension were performed using CM and TM strips isolated from bovine,
rabbit and monkey.
RESULTS. Topical application of 0.5% Y-27632 and 0.05% Y-39983
significantly decreased the IOP, with maximum decreases of 6.9 and 9.6 mmHg,
respectively, compared with the control eye. Both compounds dose-dependently
induced the relaxation of rabbit CM which was previously constricted with
carbachol. Both compounds also showed activity to significantly relax the
bovine CM, while they had little effect on monkey CM constriction. Y-27632 and
Y-39983 were also tested on bovine TM strips. Both ROCK inhibitors had
significant relaxing activity.
CONCLUSIONS. The present results indicate that inhibitors of ROCK act to
relax both CM and TM of the eye. Reduction of IOP by the ROCK inhibitors is
likely due to regulation of aqueous humor dynamics through a Rho-mediated
pathway in CM and TM. ROCK inhibitors could be possible agents for the
development of novel antiglaucoma drugs.