Our long-term objective has been to develop a set of noninvasive techniques for studying the physiology of the human retina. The electroretinogram (ERG), the summed activity of the retinal cells, is a noninvasive measure of retinal activity. The ERG has long been used for diagnosing and following the course of retinal diseases. By building upon discoveries made by the retinal physiologist, we have extended the usefulness of the ERG for mechanistic studies of human disease. In particular, we have developed procedures for studying both the activation and deactivation phases of phototransduction as well as for studying the activity of bipolar cells. This work has lead to numerous studies of normal and abnormal retinal activity in humans and in animal models of retinal diseases. ? ? As part of aim 1, we intend to explore possible ERG measures of ganglion cell activity. Glaucoma, one of the leading causes of blindness, affects these cells. Current behavioral and electrophysiological procedures for detecting early signs of ganglion ceil damage are less than optimal. There are considerable data from retinal physiology, and recent claims based on clinical evidence from other groups, to suggest that pattern stimuli and/or stimuli near cone ERG threshold (the photopic negative response) may provide the measure needed. We propose a way to assess these claims. ? ? As part of aim 2, we improve on the techniques we have already developed and apply them to: the study of cone deactivation in mutations known to affect the receptors, the study of inner nuclear layer activity in diseases affecting receptor transmission and/or bipolar cell responses and the study of localized diseases affecting primarily the macular region. ? ? Static perimetric visual fields and 30 Hz full-field flicker ERGs are leading candidates for primary outcome measure in trials involving diseases of the receptors (e.g. RP). We have a very poor understanding of how these measures are related either to each other or to local retinal damage. We propose as part of aim 3 to improve our understanding of these relationships as well as to improve our analysis of visual field data. ? ?
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