In a new application, an young investigator requests five years of support for studies of RPE65, an abundant microsomal associated protein. The major goal of this proposal is to determine if RPE-65 is the retinol isomerase, and if so, to characterize it's activity.
Specific Aim 1 is to express human RPE-65 and determine the role of the recombinant protein in retinoid processing.
Specific Aim 2 is to determine the amino acids in RPE-65 that are critical for its subcellular localization and retinoid processing activity.
Specific Aim 3 is to clone salamander RPE-65 and determine its cellular localization.
Specific Aim 4 is to examine the retinoid profile of RPE-65 in vivo using RPE-65 knockout mice that have been generated by a collaborator.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY012231-03
Application #
6179033
Study Section
Special Emphasis Panel (ZRG1-VISB (01))
Program Officer
Helmsen, Ralph J
Project Start
1998-07-01
Project End
2001-06-30
Budget Start
2000-07-01
Budget End
2001-06-30
Support Year
3
Fiscal Year
2000
Total Cost
$142,945
Indirect Cost
Name
Medical University of South Carolina
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425
Shin, Younghwa; Moiseyev, Gennadiy; Petrukhin, Konstantin et al. (2018) A novel RPE65 inhibitor CU239 suppresses visual cycle and prevents retinal degeneration. Biochim Biophys Acta Mol Basis Dis 1864:2420-2429
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Qiu, Fangfang; Matlock, Greg; Chen, Qian et al. (2017) Therapeutic Effects of PPAR? Agonist on Ocular Neovascularization in Models Recapitulating Neovascular Age-Related Macular Degeneration. Invest Ophthalmol Vis Sci 58:5065-5075
He, Xuemin; Cheng, Rui; Park, Kyoungmin et al. (2017) Pigment epithelium-derived factor, a noninhibitory serine protease inhibitor, is renoprotective by inhibiting the Wnt pathway. Kidney Int 91:642-657
Deng, Guotao; Moran, Elizabeth P; Cheng, Rui et al. (2017) Therapeutic Effects of a Novel Agonist of Peroxisome Proliferator-Activated Receptor Alpha for the Treatment of Diabetic Retinopathy. Invest Ophthalmol Vis Sci 58:5030-5042
Shin, Younghwa; Moiseyev, Gennadiy; Chakraborty, Dibyendu et al. (2017) A Dominant Mutation in Rpe65, D477G, Delays Dark Adaptation and Disturbs the Visual Cycle in the Mutant Knock-In Mice. Am J Pathol 187:517-527
Harper, Angelica R; Wang, Xiang; Moiseyev, Gennadiy et al. (2016) Postnatal Chick Choroids Exhibit Increased Retinaldehyde Dehydrogenase Activity During Recovery From Form Deprivation Induced Myopia. Invest Ophthalmol Vis Sci 57:4886-4897

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