neural tissue whose continued correct functioning is essential to vision. Although it is subject to both developmental and acquired dysfunction, the objective methods available to diagnose and investigate functional disorders of the retina are limited. An existing method that promises further development is the examination of the ERG, a gross electrical signal that can be recorded non-invasively from the eye and that reflects the activity of all retinal cells. However, to realize the full potential of the ERG, it is necessary to improve our understanding of the contributions made to it by the many different retinal cell types and then to devise better methods of analyzing ERG recordings to provide diagnostically useful information. This is the goal of the proposed research. The recent availability of much new information about the physiology and synaptic pharmacology of the retina will guide the main approach that will be taken. This is to identify and then characterize as fully as possible the contributions made to the ERG by pharmacologically-isolated types of neurons in inner and outer retina. The macaque monkey, with a retina very similar to that of humans, has been chosen as the best available animal model for these necessarily invasive studies whose feasibility has already been demonstrated both in primate and non-primate species. Particular emphasis will be placed on analyzing the ERG of the dark-adapted eye, and the responses to weak stimuli, partly because these involve the simpler rod-circuit that subserves scotopic vision, and partly because of recently identified inner-retinal contributions to the scotopic ERG from ganglion and amacrine cells. The role of retinal glial cells in mediating contributions of various cell types to the ERG will be examined and intraretinal recordings will complement the isolation procedures in identifying the cellular origins of ERG components. Models will be developed to describe each of the component potentials from the various cell types that are characterized, and these will be combined to provide a complete model of the ERG. The existence of such a model for the normal ERG should greatly aid in the analysis of recordings from diseased eyes. The applicability of the analyses to human recordings will be assessed in normals and in patients with pathology that affects inner retina.
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