Localization of Prostaglandin E Receptor Subtypes in the Ciliary Body of Mouse Eye

Abstract

Prostaglandin E2(PGE2) markedly reduces intraocular pressure (IOP) when applied topically and induces strong relaxation of pre-contracted isolated ciliary muscle through PGE2receptor. Because the ciliary muscle relaxation reduces IOP by enhancing uveoscleral aqueous outflow, the ciliary muscle where the existence of PGE2receptors has been demonstrated is thought to be one of the target tissues for PGE2-induced IOP reduction. To investigate the subtypes of PGE2receptors in the ciliary muscle, the regional distribution of four PGE2receptor subtypes (EP1, EP2, EP3and EP4) in the mouse ciliary body was investigated by in situ hybridization using specific probes. Consistent messenger RNA signals for EP1and EP4receptors were expressed in the ciliary muscle, although signal levels for these subtypes were less potent as compared with the kidney, which was used as a reference organ. EP2and EP3signals were not detected. Stimulation of the EP4receptor activates adenylate cyclase, which should induce ciliary muscle relaxation. Therefore, the IOP reduction induced by PGE2analogs may be mediated by the EP4receptor. In contrast, stimulation of the EP1receptor is believed to promote intracellular Ca2+mobilization, and hence should cause ciliary muscle contraction. Thus, the coexistence of EP1and EP4receptors in the ciliary muscle suggests that the regulation of ciliary muscle tone by PGE2is based on a complex mechanism involving multiple receptor subtypes.