Glaucoma is a blinding eye disease. A major treatment protocol for lowering elevated intraocular pressure is reduction of aqueous humor secretion by topical administration of B-adrenergic antagonists and other drugs. However, the basis for the clinical effectiveness of these drugs is largely unknown. It would therefore be useful to gain an understanding of the cellular and molecular events underlying reduction of aqueous inflow. A Knowledge of these event might also provide leads to improved treatment therapies for glaucoma. This revised proposal is based upon the identification of Na+,K+,Cl cotransport in bovine and fetal human ciliary epithelial cells and its detection immunologically in adult human tissue. Na+,K+,CL cotransport is required for salt and water flow in other secretory tissues, including retinal pigment epithelium, but its role in aqueous inflow is unknown. The fining that Na+, K+, Cl cotransport is stimulated by adenylyl cyclase in fetal human NPE cells could be related to stimulation of aqueous inflow in vivo by drugs known to activate adenylyl cyclase. We propose to characterize Na+, K+, Cl- cotransport in ciliary epithelium by two approaches. First, immunohistological studies using recently developed antisera against Na+, K+, Cl- cotransporters and HC03-/Cl- exchangers will aim at identifying the membrane ciliary epithelium. Second investigation of adenylyl cyclase stimulation or inhibit aqueous inflow in vivo to be evaluated against a defined, hormonally regulated ion transport system in tissue culture.
