CELLULAR PHYSIOLOGY OF OCULAR EPITHELIA

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This project will investigate the physiology and pharmacology of individual epithelial cells of the eye. The focus will be on cells of the ciliary body, which secretes the aqueous humor, and of the retinal pigment epithelium, which is necessary for the survival of the photoreceptors. The overall aim is to understand the cellular actions of neural and hormonal signals that regulate the physiology of the epithelial cells, including secretion and phagocytosis. To date, there is little information at the cellular level about these processes, but because of the central role of ocular epithelial cells in diseases of the human eye, including glaucoma and retinal degenerative disorders, an understanding of the basic physiology of these cells and how it is regulated will be vital to better understanding and treatment of ocular disease. The proposed studies will be done on single cells. Electrical techniques will be used to measure transmembrane ionic currents and to determine how the modulation of these currents controls both secretion and phagocytosis in ocular epithelial. Changes in cell membrane capacitance will be employed to monitor the changes in membrane area that accompany exocytosis and phagocytosis. In addition, fluorescent indicators will be used to measure changes in important intracellular ions, such as calcium. The electrical and fluorescence measurements can be combined within a single cell, providing powerful tools for answering questions of cellular physiology. In the ciliary body, the experiments will give information about how the secretion of the aqueous humor is regulated and thus shed light on the cellular actions of drugs used to control glaucoma. In the retinal pigment epithelium, a major goal is to understand the cellular events that lead to phagocytosis of the shed tips of photoreceptor outer segments, an event that is defective in an animal model of blindness caused by hereditary retinal degeneration.