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Reiko Yamagishi, Makoto Aihara; IOP-lowering Effect Of Prostanoid EP Receptor Agonist In Combination With FP Receptor Agonist. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3112.
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Prostanoid EP2 and EP4 receptor agonists have been reported to lower intraocular pressure (IOP). We also reported that selective agonists of EP2 and EP4 receptor reduced IOP in a dose-dependent manner in mice. However, combined effect of EP receptor agonists on IOP reduction with other ocular hypotensive agents has not been clarified. The purpose of this study is to investigate combined effect on IOP reduction by EP receptor agonists and a first-line drug, FP receptor agonist, in mouse eyes.
A single drop with 3 µl aliquots of 0.1% ONO-AE1-259 (EP2 agonist; EP2), 0.1% ONO-AE1-329 (EP4 agonist; EP4), 0.005% latanoprost(FP agonist; LAT)and 5% DMSO as a vehicle solution (DMSO) were topically applied into randomly selected one of two eyes in ddY mouse. To clarify combined effect of EP2 and EP4 with LAT, LAT or DMSO was concomitantly applied 30 min before application of DMSO, LAT, EP2 or EP4. Two hours later, IOP was measured with a microneedle method and IOP reduction was evaluated by the difference between IOP of the treated eye and that of the contralateral control eye.
IOP reduction by a single application of DMSO, EP2, EP4 and LAT were -0.8%, 9.8%, 7.8%, and 17.3%, respectively. EP2, EP4 and LAT significantly reduced IOP (p<0.01 v.s. DMSO by Dunnett test, n=10). IOP reduction by a concomitant administration of LAT/EP2, LAT/EP4, LAT/LAT, LAT/DMSO and DMSO/DMSO were 17.1%, 23.8%, 18.3%, 15.2%, and 1.4%, respectively. Among them, LAT/EP4 showed significant more IOP reduction than LAT/DMSO. (p<0.05 )
Additive effect on FP agonist-induced IOP reduction was induced by EP4 agonist, but not by EP2 agonist in mice. EP4 agonist may be expected to be a useful therapeutic agent for IOP reduction in combination with FP agonist.
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