The investigators' 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, they have shown that the usefulness of the ERG can be extended. Their initial observation that the leading edge of the rod a-wave could be described by the same models fitted to single receptor recordings has led to numerous studies of normal and abnormal retinal activity in humans and in animal models of retinal diseases. As part of aim 1 (INNER RETINA, MF-ERG), they propose to examine the contribution of the inner retina, which includes amacrine and ganglion cells, to a local measure of retinal activity, the cone multifocal ERG. Glaucoma, one of the leading causes of blindness, affects these cells. Current behavioral and electrophysiological procedures for detecting early signs of retinal damage are less than optimal. The investigators believe that they have found a very promising approach to this problem. The approach includes studies involving: a. monkeys in which inner retinal activity is pharmacologically blocked, b. normal human subjects, c. patients with glaucoma, and d. mathematical and statistical work. During the current grant period, they have developed procedures for measuring the response of the human rod receptor and for studying rod on-bipolars.
Aim 2 (UTILIZE TECHNIQUES DEVELOPED IN CURRENT GRANT PERIOD) is to study the activity of the normal and abnormal human rod on-bipolar with these techniques. Further, they will develop a technique for measuring the waveform of the cone photoreceptor response (that is, deactivation) and will use it to study light adaptation and retinal diseases of the cone system.
A third aim (DEVELOP TECHNIQUES FOR ASSESSING INL ACTIVITY IN NL AND ABN RETINAS) is to develop techniques for assessing inner nuclear layer (INL) activity of normal and abnormal retinas. While knowledge of the rod ERG is approaching the point where a computational model may be feasible, in comparison, less in known about the contributions of the bipolar cells to the human cone ERG. Here the investigators attack this problem with studies involving: a. monkeys in which INL activity is pharmacologically dissected, b. normal human subjects, c. patients with disease of the INL, and d. mathematical work.
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