VOLUME REGULATION IN NORMAL AND CATARACTOUS LENSES

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We wish to understand the normal physiological properties of the lens and how these properties confer the ability to regulate cellular volume and thereby maintain transparancy. Moreover, the lens sits between the aqueous and vitreous where it likely has some role in controlling the composition of these two humors. In certain circumstances the lens losses its ability to control cell volume and the composition of the intracellular milieu, whereupon a cataract is formed. We hope to understand those changes in normal physiological properties which underlie the loss of transparancy. Because the lens is a syncytial tissue, there are some special proglems in understanding its normal physiological properties. There appears to be more than one type of cell in the lens but, because it is a snycytium, transport by one type of cell in one location affects the composition of cytoplasm and membrane fluxes in other types of cells in other locations. Thus, to understand the overall macroscopic properties of the lens we must characterize the more microscopic properties of: (i) the membrane transport properties; (ii) the spatial localization of these membrane transport parameters; (iii) the interconnection of lens cells by low resistance gap junctions; and (iv) the small extracellular path between lens fiber cells. In order to characterize these microscopic properties, we propose to utilize intracellular microelectrodes to study voltage, hydrostatic pressure and ionic composition of the cytoplasm. Moreover, we will use impedance techniques to characterize the passive paths for current flow and how some of these paths are regulated (e.g., gap junctional conductance or membrane conductance). We will study extracellular currents, both natural and induced, using large area patch pipettes and the vibrating probe. And we will isolate the anterior epithelium as well as fiber cell membrane vesicles to study their transport properties. Lastly, we will use structurally based computer models of the lens to relate the microscopic properties to the overall macroscopic physiological properties.