The proposed experiments are designed to utilize a vertebrate genetic system capable of identifying dominant mutations affecting the zebrafish retina, with particular emphasis on mutations involved in rhodopsin trafficking. The long-term objectives of the proposed research include the identification of genes associated with blindness caused by age-related retinal degeneration and the characterization of the cellular and molecular mechanisms underlying retinal degeneration. Mutations causing dominantly inherited night blindness will be isolated by a behavioral assay and confirmed by histological and physiological methods. Proper rhodopsin localization and transport will be evaluated by breeding mutant zebrafish with transgenic zebrafish that express a transgene encoding a rhodopsin-green fluorescent protein (GFP) fusion protein and examining the progeny by confocal fluorescent microscopy. Additional characterization of other transport systems within the photoreceptors of mutant fish will elucidate possible interactions between cellular transport mechanisms. Finally, identification of the genes responsible for these mutations will be achieved by positional cloning strategies. The proposed work will provide insight to the mechanisms underlying photoreceptor cell death that ultimately lead to retinal degeneration and blindness associated with aging.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32EY013502-01
Application #
6339423
Study Section
Special Emphasis Panel (ZRG1-MDCN-1 (20))
Program Officer
Dudley, Peter A
Project Start
2001-06-01
Project End
Budget Start
2001-06-01
Budget End
2002-05-31
Support Year
1
Fiscal Year
2001
Total Cost
$34,832
Indirect Cost
Name
Harvard University
Department
Microbiology/Immun/Virology
Type
Schools of Arts and Sciences
DUNS #
071723621
City
Cambridge
State
MA
Country
United States
Zip Code
02138
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Song, Ping; Dudinsky, Lynn; Fogerty, Joseph et al. (2016) Arl13b Interacts With Vangl2 to Regulate Cilia and Photoreceptor Outer Segment Length in Zebrafish. Invest Ophthalmol Vis Sci 57:4517-26
Wasfy, Meagan M; Matsui, Jonathan I; Miller, Jessica et al. (2014) myosin 7aa(-/-) mutant zebrafish show mild photoreceptor degeneration and reduced electroretinographic responses. Exp Eye Res 122:65-76
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Perkins, Brian D; Nicholas, Claire S; Baye, Lisa M et al. (2005) dazed gene is necessary for late cell type development and retinal cell maintenance in the zebrafish retina. Dev Dyn 233:680-94
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