Abstract
To investigate the ocular hypotensive effect and change of outflow facilities by prostaglandin E2 (PGE2) and selective agonists of PGE2 receptor subtypes (EP1, -2, -3, -4) using C57BL/6 (wild-type [WT]) mice or FP, EP1, -2, and -3 receptor-deficient mice. IOP was measured with a microneedle, and IOP reduction was evaluated by the difference in IOP between the treated eye and the contralateral control eye. The time course and dose dependency of IOP reduction with PGE2 and the four selective EP receptor agonists were assessed. Aqueous humor outflow facility was measured by a two-level constant-pressure perfusion PGE2, ONO-AE1-259-01 (EP2 agonist), and ONO-AE1-329 (EP4 agonist) significantly reduced IOP in a dose-dependent manner, whereas ONO-DI-004 (EP1 agonist) and ONO-AE-248 (EP3 agonist) had no effect. Peak IOP reduction at 2 hours with 0.1% ONO-AE1-259-01 (EP2 agonist) and ONO-AE1-329 (EP4 agonist) were 21.1% +/- 4.8% and 17.5% +/- 2.9%, respectively (P < 0.01). IOP reduction with ONO-AE1-259-01 (EP2 agonist) was completely eliminated in EP2 knockout mice, but IOP reduction in other knockout mice was similar to that observed in WT mice. The effects of ONO-AE1-259-01 (EP2 agonist) and ONO-AE1-329 (EP4 agonist) on the outflow f...Continue Reading
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