Specific genetic defects are responsible for a variety of retinal degeneration diseases that affect human populations. The goal of this research program is to characterize analogous defects in the invertebrate Drosophila melanogaster. In Drosophila, it is possible to combine molecular, genetic, physiological techniques to gain a better understanding of the altered cellular activities that underlie these diseases. Many Drosophila mutants previously identified by their effects on the process of visual transduction also show defects in photoreceptor maintenance. Mutants in the gene coding for the visual pigment rhodopsin show an age dependent loss of the microvillar membranes that form the rhabdomere of the photoreceptors. A large sample of defined mutants in the rhodopsin protein have been generated: these are likely to affect the stability of the protein, the potential of the protein to be glycosylated, or the positioning of the protein in the membrane. An immunohistochemical approach will investigate the mechanisms by which these rhodopsin mutants affect rhabdomere structure. Each of these mutant rhodopsins also will be - expressed in an in-vitro system to investigate the inherent stability and retinal binding capacity of the modified rhodopsin proteins. A newly identified gene, mda, plays a critical role in the structure and function of the photoreceptors. Mutants in this gene are defective in visual transduction and also show disarranged microvillar structures on the cytoplasmic face of the rhabdomeres. This region is the subcellular site of rhabdomeric membrane renewal and also likely the location of molecular events underlying the phototransduction response. Molecular characterization of this gene will address the role of the encoded gene product in photoreceptor maintenance and function. rdgC has a mutant phenotype that is similar to the inherited retinal degeneration syndromes that affect human populations. That is, there is no obvious defect in visual processes before the onset of retinal degeneration. Light stimulation of rhodopsin triggers degeneration in rdgC mutants. Therefore, the rdgC gene product acts to prevent retinal degeneration that occurs as a consequence of normal rhodopsin activity not directly involved in the phototransduction pathway. To deduce the normal function of the rdgC protein in photoreceptors, we will use molecular techniques to characterize the rdgC gene and gene product. Genetic strategies will be used to identify additional components that act in concert with rdgC to maintain photoreceptor structure.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY006808-06
Application #
3263473
Study Section
Genetics Study Section (GEN)
Project Start
1987-07-01
Project End
1995-06-30
Budget Start
1992-07-01
Budget End
1993-06-30
Support Year
6
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Notre Dame
Department
Type
Schools of Arts and Sciences
DUNS #
824910376
City
Notre Dame
State
IN
Country
United States
Zip Code
46556
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