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Abstract #6867 Published in IGR 4-1
Reduction of intraocular pressure by topical administration of an inhibitor of the Rho-associated protein kinase
Waki M; Yoshida Y; Oka T; Azuma MCurrent Eye Research 2001; 22: 470-474
PURPOSE: Rho-associated coiled coil-forming protein kinase (ROCK) is a downstream target of a small GTPase, Rho. This 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 the regulation of intraocular pressure (IOP), while that of ocular vessels could affect blood flow to retina. The present study was performed to investigate the effect of a ROCK inhibitor on IOP in rabbits. METHODS: Y-27632, an inhibitor of ROCK, was dissolved in an ophthalmic solution and topically administered to the eye of a Japanese white rabbit. IOP 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 IOP, with maximum decreases of 5.3 and 4.3 mmHg after 90 minutes compared to the control eye. Y-27632 inhibited the carbachol-induced constriction of rabbit ciliary muscle. CONCLUSIONS: The ROCK inhibitor reduced IOP 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. These results suggest that the ROCK inhibitor is a promising treatment for next generation glaucoma therapy.
Dr. M. Waki, Research Laboratory, Senju Pharmaceutical Co., Ltd., 1-5-4 Murotani, Nishi-ku, Kobe 651-2241, Japan. mitsunori-waki@senju.co.jp
Classification:
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
