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T. Saeki, H. Tsuruga, M. Aihara, M. Araie, K. Mizuno, Y. Hattori; A Potential of Rho-Associated Coiled-Coil-Forming Kinase Inhibitor in Reduction of Murine IOP. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4812.
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© ARVO (1962-2015); The Authors (2016-present)
Rho-associated coiled-coil-forming kinase (ROCK) inhibitors are reported to decrease intraocular pressure (IOP) in rabbit eyes and supposed to regulate IOP in monkey and human eyes through relaxation of trabecular meshwork and ciliary muscle. In this study, IOP-lowering effect of a ROCK inhibitor and its synergistic effect with latanoprost are investigated using mouse eyes.
A ROCK inhibitor (K115) was prepared as 0.5% solution. C57BL/6J mice were acclimatized under the 12-hour light-dark cycle (6:00 on 18:00 off) for at least 2 weeks before experiments. Three micro liters of the solution was topically applied once into one of two eyes in a blind manner at 18:00. The fellow eyes were untreated. IOP was measured by a microneedle method. At 0.5, 1, 2, and 4 hours after the administration, the IOP-lowering effect was calculated as the difference between IOP in the treated eye and that in the contralateral untreated eye. (n=5-6 for each time point) 0.125, 0.25, and 0.5% K115 were used to examine dose-dependent response in IOP reduction. (n=7-10 for each dose) Next, the additional IOP-lowering effect of K115 to latanoprost was examined. 0.25% K115 was applied 2 hours after the administration of 0.005% latanoprost, then further 30 minutes later IOP was measured. (K115/latanoprost group) As a control group, IOP was measured 2.5 hours after the administration of 0.005% latanoprost without K115. (latanoprost group) The IOP reductions in the two groups were compared. (n=6 for each group)
0.5% K115 solution showed maximum IOP reduction by 29.6±4.3% in 30 minutes after the administration. 0.125, 0.25, and 0.5% K115 revealed significant IOP reduction (p<0.01) in a dose-dependent manner by 17.9±6.7%, 22.1±2.7% and 30.5±3.7%, respectively. IOP reduction in K115/latanoprost group (37.3±6.4%) was significantly higher than that in latanoprost group (24.8±4.1%).(p<0.01)
A ROCK inhibitor (K115) significantly reduced mouse IOP and also showed a significant additive effect on latanoprost-induced IOP reduction. K115 may have a therapeutic potential for glaucoma.
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