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M. Aihara, T. Saeki, T. Ota, M. Araie; Mouse Intraocular Pressure–Lowering Effect With Prostanoid EP Receptor Agonists . Invest. Ophthalmol. Vis. Sci. 2006;47(13):424.
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Prostaglandin F2alpha analogues are widely used to lower intraocular pressure (IOP), mainly through prostanoid FP receptor. However, other prostanoid receptors such as EP or DP may be also related to IOP–lowering. In this study, the IOP–lowering effect of specific agonists for EP1, 2, 3, and 4 subtypes of PGE2 receptor were investigated using mouse eyes.
EP1, 2, 3, and 4 specific agonists (ONO–DI–004, AE1–259, AE–248, and AE1–329) were prepared as 0.1% solutions including 5% DMSO. C57BL/6J mice were acclimatized under the 12–hour light–dark cycle (6:00 on 18:00 off) for at least 2 weeks before experiments. Three micro litters of each agonist solutions were topically applied once into one of two eyes in a blind manner at 18:00. The fellow eye treated with vehicle (5% DMSO) was served as control. IOP was measured by a microneedle method. The IOP–lowering effect of each drug at 2.5 hours after the administration was calculated as the difference in IOP and reduction in IOP from the IOP of the non–treated fellow eye.(n=8 for each agonist)
EP1 and EP3 agonists had no significant IOP–lowering effect, whereas EP2 and EP4 agonists significantly reduced IOP by 21.1Ã‘Â±6.4% and 7.5Ã‘Â±5.5%, respectively.(p<0.01:EP2, p<0.05:EP4) EP2 receptor deficient mice were used to confirm the presence of receptor–mediated IOP–lowering effect by EP2 agonist (n=9). EP2 agonist could not reduce IOP in EP2 receptor deficient mice. EP4 receptor deficient mice were not available because of embryonic leathality.
EP2 agonist has a potential to reduce IOP in mouse eyes through its own receptor. Prostanoid EP2 receptor may become a therapeutic target for IOP reduction.
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