This project is designed to elucidate aspects of retinal function concerned with ionic homeostasis, the role of glial cells, and the generation of the electroretinogram (ERG). Our specific objectives are: (1) To determine the sources and sinks of current underlying components of the ERG--by applying a quantitatively thorough current-source-density (CSD) analysis; (2) To determine the sources and sinks of changes in the extra-cellular concentration of ions--by applying a newly-developed technique of ion-source-density (ISD) analysis; (3) To assess the cellular origins, whether neural or glial, of ERG components and extracellular ionic changes--by experiments with selected pharmacological agents that may serve to dissociate various responses; (4) To specify the resting levels of, and the light-evoked changes in, the concentrations of various ions in the retina--by measurements with ion-selective microelectrodes (ISM's) in vivo and in vitro; (5) To examine characteristics of the distal K-increase (OPL K-increase) and determine its relationship to the b-wave--by comparative analyses of both responses and the effects of stimulus variables and pharmacological agents; and (6) To investigate the ability of Muller cells in whole retinas to spatially buffer changes in [K+]. The proposed experiments will aid in clarifying questions concerning the origin or ERG components, and thereby further the interpretative utility of the ERG in clinical ophthalmological diagnosis. This work will also contribute to our understanding of glial cells, and of the role and influence of the extracellular micro-environment in neuronal-glial interactions.
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