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Tomohiro Karakawa, Shinsaku Yamane, Yoshikazu Goto, Yasuo Ochi, Yasushi Hirota; Effect of ONO-9054 on Aqueous Humor Dynamics in Monkeys. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1974.
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© ARVO (1962-2015); The Authors (2016-present)
ONO-9054 (Ono Pharmaceuticals, Osaka Japan) is a novel dual EP3/FP agonist that is currently in development for the treatment of ocular hypertension and glaucoma. The purpose of this study was to investigate the effect of ONO-9054 on aqueous humor dynamics in monkeys.
Aqueous humor flow was measured with a fluorophotometer in 15 monkeys per group that received unilateral ocular administration of vehicle, timolol (5000 μg/mL), latanoprost (50 μg/mL) or ONO-9054 (3, 10, or 30 μg/mL). Outflow facility was determined using a two-level, constant pressure perfusion method in 10 monkeys per group that received unilateral ocular administration of latanoprost (50 μg/mL) or ONO-9054 (3, 10, or 30 μg/mL) in one eye and vehicle in the contralateral eye. Uveoscleral outflow was measured by perfusion the anterior chamber using FITC-labeled dextran in 8 monkeys per group that received unilateral ocular administration of latanoprost (50 μg/mL) or ONO-9054 (30 μg/mL) in one eye and vehicle in the contralateral eye.
Timolol decreased the aqueous humor flow (0.88 ± 0.06 μL/min) relative to vehicle (1.50 ± 0.09 μL/min). On the other hand, aqueous flow was essentially unperturbed relative to the vehicle treated eye by ONO-9054 at 3, 10, and 30 μg/mL (1.65 ± 0.12 μL/min, 1.45 ± 0.11 μL/min, and 1.59 ± 0.09 μL/min) or latanoprost (1.54 ± 0.13 μL/min). When compared with the contralateral vehicle-treated eyes (0.56 ± 0.05 μL/min/mmHg), latanoprost had no effect on the outflow facility (0.63 ± 0.09 μL/min/mmHg). Likewise, ONO-9054 at 3 μg/mL had no effect on the outflow facility (0.49 ± 0.07 μL/min/mmHg). On the other hand, ONO-9054 at 10 and 30 μg/mL significantly increased outflow facility (0.72 ± 0.08 μL/min/mmHg, p < 0.01 and 0.64 ± 0.11 μL/min/mmHg, p < 0.05, respectively) relative to the contralateral vehicle-treated eyes (0.48 ± 0.05 μL/min/mmHg and 0.50 ± 0.08 μL/min/mmHg, respectively). Latanoprost and ONO-9054 at 30 μg/mL significantly increased uveoscleral outflow (0.68 ± 0.15 μL/min, p < 0.01 and 0.56 ± 0.07 μL/min, p < 0.05, respectively) relative to the contralateral vehicle-treated eyes (0.39 ± 0.06 μL/min and 0.34 ± 0.06 μL/min, respectively).
ONO-9054, a dual agonist for prostaglandin EP3 and FP receptors, increases both total outflow and uveoscleral outflow but not aqueous humor flow. This study demonstrates that ONO-9054 has dual action on aqueous outflow.
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