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K. Mizuno, M. Ohta, J. Mori, T. Ozawa, M. Nishio, H. Hidaka, K. Sawanobori; Effects of K-115, a Rho-Kinase Inhibitor, on Aqueous Humor Dynamics in Rabbits. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1640. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Previously, we have presented the ocular hypotensive effect of K-115 ophthalmic solution in rabbits and monkeys (ARVO2007). In this study, we evaluated the effect of K-115 ophthalmic solution on aqueous humor dynamics and blood-aqueous barrier in rabbits.
Male Japanese White rabbits were used. To evaluate the aqueous humor outflow, 0.4% K-115 was instilled topically into randomly-selected one eyes, and contralateral eyes were saved as control. Sixty minutes after instillation, the outflow facility or the uveoscleral outflow was measured with two-level constant pressure method or FITC-Dextran perfusion method, respectively. To analyze the effect of K-115 on blood-aqueous barrier functions, 1% K-115 was instilled 4 times at 1 hour interval and the protein concentration in the aqueous humor was measured.
In the outflow facility study, K-115 showed significant ocular hypotensive effect compared to contralateral eyes (13.7 ± 1.0 vs. 22.5 ± 0.5 mmHg, p = 0.0017, n = 6). The outflow facility was increased compared to contralateral eyes (0.241 ± 0.044 vs. 0.130 ± 0.014 µL/min/mmHg, p = 0.037). In the uveoscleral outflow study, K-115 decreased the intraocular pressure (12.7 ± 1.1 vs. 20.7 ± 0.9 mmHg, p = 0.0002, n = 6) however, had no effect on uveoscleral flow compared to the contralateral eyes (0.353 ± 0.032 vs. 0.295 ± 0.036 µL/min, p = 0.26). Although, four times instillation of 1% K-115 showed significant ocular hypotensive effect (8.3 ± 0.4 vs. 21.7 ± 3.2 mmHg, p = 0.014), no effect was found on aqueous humor protein concentration (3245.1 ± 260.0 vs. 3153 ± 322.1 µg/mL, p = 0.836).
Topical instillation of K-115 decreased the intraocular pressure by increasing the outflow facility. Additionally, repeated instillation of K-115 had no effect on the blood-aqueous barrier. These results suggest that K-115 ophthalmic solution may be a useful therapeutic agent for the treatment of glaucoma.
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