This research program concerns several fundamental aspects of the interrelationships between cone photoreceptors and the pigments they contain and neural organization and visual behavior. These issues will be pursued using two important animal models. One line of investigation involves the mouse, a preeminent animal model for studies of retinal physiology and retinal disease. A new transgenic mouse in which the X-linked M-opsin gene has been replaced by a human L-opsin gene will be studied in a series of experiments. These animals allow the possibility of examining how a retina and visual system can potentially accommodate to a new dimension of visual information. To evaluate this issue, noninvasive electrophysiological and behavioral experiments will be conducted on these transgenic mice to (1) seek functional validation of the transgenic manipulation, (2) make comparisons of signals originating from native and transgenic photopigments and their combinations, and (3) examine to what extent functional vision has been altered by the addition of a novel photopigment, including the possibility that a new dimension of color vision may emerge. Two investigations of vision and its mechanisms in wild type mice will also be conducted. One seeks to determine whether or not the co-expression of UV and M pigments in mouse cones obviate the possibility of dichromatic color vision; the other uses ERG and behavioral measures to examine changes in mouse visual sensitivity across the lifespan. A second major effort involves the development of a nonhuman model for examination of the dynamics of retinal detachment. Most animal models used to date have rod dominated retinas. In recognition of the fact that retinal detachment in humans can have its greatest impact on cone-based vision, the ground squirrel, a rodent with a heavily cone-dominated retina, will be developed as a vehicle to examine retinal detachment. Three specific goals will be pursued: (1) a unique ERG index will be used to examine the dynamics of surgical detachment and reattachment of the retina, (2) the effects of supplementary oxygen given immediately post-detachment will be investigated as a possible means of ameliorating the degenerative effects initiated by retinal detachment, and (3) the model will be used to investigate whether the losses in blue-yellow color vision often reported as a consequence of retinal detachment can be traced to greater vulnerability of the S cones. ? ?
Showing the most recent 10 out of 64 publications
