Glaucoma is a blinding eye disease. A major treatment strategy for this disease is the reduction of aqueous humor secretion with B-adrenergic antagonists such as timolol and other drugs. Although such treatments are effective, their molecular mechanisms are largely unknown. An understanding of ion transport mechanisms which underlie aqueous humor secretion and its regulation might lead to improved glaucoma treatment protocols. Considerable evidence suggests that timolol may function as a hypotensive agent by inhibiting diurnal adrenergic elevation of aqueous humor inflow. The PI has reported that Na+, K+, Cl cotransport in ciliary epithelium is stimulated by B adrenergic agents and inhibited by timolol. This is a promising lead in understanding diurnal adrenergic regulation of aqueous humor inflow in humans. The PI proposes to investigate the molecular mechanisms underlying stimulation of Na+, K+, Cl cotransport by adrenergic agonists, including the roles of second messenger pathways and phosphorylation dephosphorylation pathways. He also proposes to test the hypothesis that other hormones known to either increase or decrease aqueous inflow might exert their effects through modulation of Na+, K+, Cl cotransport activity.
