The overall goal of proposed research is to gain further knowledge of the physiology and pharmacology of aqueous outflow in the human eye.In proposed studies, the investigators have chosen to look at two general classes of drugs used therapeutically in the treatment of glaucoma; adrenergic agents and cholinergic agents.
The specific aims are to characterize outflow facility responses to these drugs in her recently described human isolated outflow pathway perfusion model, to map the distribution of drug receptors in outflow tissues, and to characterize relevant second messenger systems. This three-pronged approach, coordinating studies in physiology, biochemistry, and molecular biology, has the potential for producing a wealth of information greater than the sum of each individual approach in isolation. Recent refinements in molecular biology techniques and their applications is revolutionizing the diagnosis and treatment of disease, as well as basic medical research. The investigator's hope that her approach, using this powerful new technology in conjunction with the human TM model will allow her to develop a composite map of the human outflow system which will localize groups of cells which mediate changes in outflow resistance and characterize the second messenger systems which are coupled to these changes. Enhanced understanding of the basic mechanism(s) underlying normal outflow physiology may lend new insight into the pathogenesis of primary open angle glaucoma, and probably will facilitate the development of more effective, specific, and safe antiglaucoma drugs.
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