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Tomohiro Karakawa, Shinsaku Yamane, Yoshikazu Goto, Masafumi Sugitani, Yasushi Hirota; Effect of ONO-9054 on Aqueous Humor Dynamics in Monkeys. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2899.
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© ARVO (1962-2015); The Authors (2016-present)
ONO-9054 (Ono Pharmaceuticals, Osaka Japan) is a novel prodrug compound with dual FP/EP3 agonist activity 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 cynomolgus monkeys.
In one set of studies ophthalmic vehicle, timolol (5000 μg/mL), latanoprost (50 μg/mL) or ONO-9054 (3, 10, or 30 μg/mL) was administered topically in a 30μL volume once into each eye. Aqueous humor flow was measured with a fluorophotometer and intraocular pressure (IOP) was measured with an applanation pneumatonometer in 15 monkeys per group. In a second set of studies outflow facility was determined using a two-level, constant-pressure perfusion method and IOP was measured in 10 monkeys per group that received unilateral ocular administration of Latanoprost (50 μg/mL) or ONO-9054 (3, 10, or 30 μg/mL) and an ophthalmic vehicle solution in the contralateral eye.
Timolol, latanoprost, and ONO-9054 reduced IOP. 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 humor 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).
ONO-9054, a dual agonist for prostaglandin FP and EP3 receptors, increases total outflow but not aqueous humor flow. This study demonstrates that the mechanism of IOP-lowing for ONO-9054 appears to involve an enhancement of outflow through both conventional and uveoscleral pathways.
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