G protein coupled receptors and ion channels in the eye: Therapeutic targets in glaucoma

In the mammalian eye, intraocular pressure is determined by the rate of aqueous inflow and the resistance to outflow. Elevated intraocular pressure is a major risk factor in glaucoma, a blinding eye disease. Drugs used to treat glaucoma either inhibit the secretion of aqueous humor by the ciliary epithelium or increase outflow of aqueous humor via various routes. The proposed research is directed at understanding the pharmacology of aqueous humor secretion and outflow in the mammalian eye. Our aims are to identify the molecular signaling pathways (G protein coupled) modulating fluid secretion by ciliary epithelial cells, as well as the cellular mechanisms underlying contractility of cells in the trabecular meshwork outflow pathway of the eye. This research will provide a greater understanding of the physiology and pharmacology of aqueous humor production and drainage, as well as the sites and mechanisms of action of ocular hypo- and hypertensive drugs. This information is required to successfully develop newer and more selective therapies to treat eye diseases such as glaucoma.