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.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY010332-02
Application #
2164136
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1993-12-01
Project End
1997-11-30
Budget Start
1994-12-01
Budget End
1995-11-30
Support Year
2
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Dunn, J J; Lytle, C; Crook, R B (2001) Immunolocalization of the Na-K-Cl cotransporter in bovine ciliary epithelium. Invest Ophthalmol Vis Sci 42:343-53
Hochgesand, D H; Dunn, J J; Crook, R B (2001) Catecholaminergic regulation of Na-K-Cl cotransport in pigmented ciliary epithelium: differences between PE and NPE. Exp Eye Res 72:1-12
Bildin, V N; Yang, H; Crook, R B et al. (2000) Adaptation by corneal epithelial cells to chronic hypertonic stress depends on upregulation of Na:K:2Cl cotransporter gene and protein expression and ion transport activity. J Membr Biol 177:41-50
Crook, R B; Takahashi, K; Mead, A et al. (2000) The role of NaKCl cotransport in blood-to-aqueous chloride fluxes across rabbit ciliary epithelium. Invest Ophthalmol Vis Sci 41:2574-83
Riese, K; Beyer, A T; Lui, G M et al. (1998) Dopamine D1 stimulation of Na+,K+,Cl- cotransport in human NPE cells: effects of multiple hormones. Invest Ophthalmol Vis Sci 39:1444-52
Crook, R B; Riese, K (1996) Beta-adrenergic stimulation of Na+, K+, Cl- cotransport in fetal nonpigmented ciliary epithelial cells. Invest Ophthalmol Vis Sci 37:1047-57