Effects of Rho-associated. protein kinase inhibitor Y-27632 on intraocularpressure and outflow facility

PURPOSE. TO elucidate the roles of Rho-associated protein kinase (ROCK) in regulating intraocular pressure (IOP) and outflow facility in the rabbit ey e. METHODS. A specific ROCK inhibitor Y-27632: was used. The IOP, the outflow facility, and the pupil diameter were determined before and after the topic al, intracameral, or intravitreal administration of Y-27632 in rabbits. Wes tern blot analysis was used to identify specific ROCK isoform in human trab ecular meshwork (TM) cells and bovine ciliary muscle (CM) tissues. The cell morphology and distribution of actin filaments and vinculin in TM cells we re studied by cell biology techniques. Carbachol (Cch)-induced contraction of isolated bovine Chi strips after administration of Y-27632 mas measured in a perfusion chamber. RESULTS. In rabbit eyes, administration of Y-27632 resulted in a significan t decrease in IOP in a dose-dependent manner. An increase of the outflow fa cility and pupil size dilation was also observed in Y-27632-treated eyes. W estern blot analysis revealed the presence of p160ROCK in human TM cells an d bovine CM tissues, in cultured human RM cells, exposure to Y-27632 caused retraction and rounding of cell bodies as well as disruption of actin bund les and impairment of focal adhesion formation. Y-27632 in addition inhibit ed Cch-induced contraction of isolated bovine CM strips. CONCLUSIONS. Administration of Y-27632 caused a reduction in IOP and an inc rease in the outflow facility. The in vitro experiments suggest that the IO P-lowering effects of Y-27632 may be related to the altered cellular behavi or of TM cells and relaxation of Chi contraction. These studies suggest tha t ROCK inhibitors may have great potential to be developed for treatment of glaucoma and other ocular diseases.