Localization and molecular signaling pathways of prostaglandin receptor subtypes in the eye

Abstract

The eicosanoids are derived from membrane fatty acids. Prostaglandins (PGs), produced from the metabolism of arachidonic acid, are members of the eicosanoid family. Prostaglandins exert a broad range of biological effects by interacting with plasma membrane-bound receptors that are coupled to guanine nucleotide-binding proteins (G proteins). The topical application of prostaglandins results in a long-lasting reduction in intraocular pressure (IOP) in mammalian eyes, including humans. The distribution and function of the prostaglandin receptor subtypes within the eye are not clearly understood. The studies presented in this dissertation are focused at addressing three specific aims which have been designed to test the following hypothesis; that prostaglandin receptors are involved in the maintenance of intraocular pressure through the modulation of aqueous humor production and in the regulation of aqueous humor outflow pathways. Subtype selective antibodies to the individual prostanoid receptors have been generated to enable the study of these receptors at the tissue, cellular and molecular level. Utilization of the antibodies and a series of pharmacological and molecular techniques have identified specific prostanoid receptor subtypes in areas of the eye which are involved in the regulation of IOP. The functional responses obtained in primary cultures of human trabecular meshwork and bovine ciliary epithelium provide evidence for the involvement of selective prostanoid receptor subtypes in the regulation of both aqueous humor production and aqueous humor outflow.