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Abstract #23942 Published in IGR 11-2
Effects of prostanoid EP agonists on mouse intraocular pressure
Saeki T; Ota T; Aihara M; Araie MInvestigative Ophthalmology and Visual Science 2009; 50: 2201-2208
See also comment(s) by Achim Krauss •
PURPOSE: 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. METHODS: 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 METHOD: RESULTS: 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 facility were similar to those of their carrier. CONCLUSIONS: EP2 and EP4 receptors mediated IOP reduction in mice, whereas the contribution of EP1 and EP3 receptors was insignificant. The EP2 and EP4 receptor-mediated mechanisms of IOP reduction were different from those mediated by the FP receptor.
Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan.
Classification:
11.4 Prostaglandins (Part of: 11 Medical treatment)
6.1.3 Factors affecting IOP (Part of: 6 Clinical examination methods > 6.1 Intraocular pressure measurement; factors affecting IOP)
5.1 Rodent (Part of: 5 Experimental glaucoma; animal models)
