Human hereditary retinal degenerations are poorly understood diseases that begin in early, middle or late life and frequently procede to total blindness. Syndromes such as retinitis and age- related maculopathy are the most common disorders in the class of diseases. Experiments are proposed to elucidate the cause of blindness in an animal model for the human diseases. This model, the rd, or retinal degenerate strain of chickens, exhibits a recessive mode of genetic transmission of a defect that leads to blindness early in life. The lesion begins as a locus in the posterior fundus, spreads peripherally, has accompanying pigmentary changes and the visual cells die after electrophysiological tests show them defective. Therefore, this model is useful as a surrogate for studying human syndromes. Preliminary studies suggest that the defect causing blindness in rd chicks is at the level of visual transduction: the conversion of light energy to electrical impulse. Studies proposed in the current grant are aimed at examining several processes involved in visual transduction. Oxidative metabolism and visual pigment bleaching will be examined by the nitroblue tetrazolium histochemical reaction and the early receptor potential, respectively. Presence or absence of specific retinal proteins (such as visual pigment proteins and G-protein, will be examined by immunocytochemistry and protein separation techniques. We will determine if rhodopsin is phosphorylated in response to light and compare cylic nucleotide levels in the mutants to those in normally sighted chicks. Opsin synthesis and outersegment renewal will be examined biochemically and anatomically. Finally, the Na-K- ATPase molecule, which controls an important membrane ion pump in photoreceptors will be analyzed, as a possible cause/effect of the blindness. These experiments will provide insight into the cause of blindness and into the normal processes of visual transduction.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY004590-06
Application #
3259045
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1984-04-01
Project End
1992-03-31
Budget Start
1989-04-01
Budget End
1990-03-31
Support Year
6
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Florida
Department
Type
Schools of Medicine
DUNS #
073130411
City
Gainesville
State
FL
Country
United States
Zip Code
32611
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Ulshafer, R J; Clausnitzer, E L; Sherry, D M et al. (1990) Immunocytochemical identification of outer segment proteins in the rd chicken. Exp Eye Res 51:209-16
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Semple-Rowland, S L; Ulshafer, R J (1989) Analysis of proteins in developing rd (retinal degeneration) chick retina using two-dimensional gel electrophoresis. Exp Eye Res 49:665-75
Ulshafer, R J; Heaton, M B (1989) Axonal transport and central visual projections of ganglion cells in congenitally blind chickens. Curr Eye Res 8:321-7
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Allen, C B; Ulshafer, R J; Ellis, E A et al. (1987) Scanning electron microscopic analysis of intraocular ossification in advanced retinal disease. Scanning Microsc 1:233-9
Ulshafer, R J; Meyer, E M (1987) Studies on putative neurotransmitters in an animal model of hereditary blindness. Prog Clin Biol Res 247:407-22

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