May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Effects of K-115, a Rho-Kinase Inhibitor, on Aqueous Humor Dynamics in Rabbits
Author Affiliations & Notes
  • K. Mizuno
    Pharmacology Tokyo Res Labs, Kowa Company Ltd, Higashimurayama, Japan
  • M. Ohta
    Pharmacology Tokyo Res Labs, Kowa Company Ltd, Higashimurayama, Japan
  • J. Mori
    Pharmacology Tokyo Res Labs, Kowa Company Ltd, Higashimurayama, Japan
  • T. Ozawa
    Pharmacology Tokyo Res Labs, Kowa Company Ltd, Higashimurayama, Japan
  • M. Nishio
    D. Western Therapeutics Institute, Nagoya, Japan
  • H. Hidaka
    D. Western Therapeutics Institute, Nagoya, Japan
  • K. Sawanobori
    Pharmacology Tokyo Res Labs, Kowa Company Ltd, Higashimurayama, Japan
  • Footnotes
    Commercial Relationships  K. Mizuno, Kowa Co., Ltd., E; M. Ohta, Kowa Co., Ltd., E; J. Mori, Kowa Co., Ltd., E; T. Ozawa, Kowa Co., Ltd., E; M. Nishio, DWTI, E; H. Hidaka, DWTI, E; K. Sawanobori, Kowa Co., Ltd., E.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 1640. doi:https://doi.org/
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    • Get Citation

      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)

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Abstract

Purpose: : 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.

Methods: : 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.

Results: : 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).

Conclusions: : 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.

Keywords: intraocular pressure • outflow: trabecular meshwork • drug toxicity/drug effects 
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