Age related macular degeneration (AMD) is the leading cause of vision loss and blindness in individuals over age 65 in the developed world. While the cellular mechanism causing AMD remains unclear, evidence from basic research and epidemiological studies suggest that oxidative tissue injury plays a major role in the pathogenesis of the disease. In this proposal, we will test the hypothesis that the pathogenesis of AMD involves oxidative damage to proteins and lipids of the retina. By optimizing clinical tissue analysis, we will be able to establish a pattern of uniquely altered proteins that distinguishes normal aging from pathologic aging in AMD. The proposed research will take a novel approach to studying the pathogenesis of AMD by using human retinal tissue, grading this tissue according to current clinical standards, analyzing the tissue with sophisticated ophthalmoscopic imaging techniques that detect oxidative injury, and utilizing proteomic technology to define retinal subproteomes for each stage of AMD. The following aims will be pursued: (1) Link the proteomics of AMD to epidemiological and clinical studies of AMD. (2) Detect and quantify lipofuscin to assess its role in the pathologic aging of AMD. (3) Develop subproteome profiles of human retinal tissue for each category of AMD. This global survey of proteins will pinpoint cellular pathways and potential subcellular mechanisms, linked to specific clinical stages that can be attributed to the disease process. This information will enable us to generate a rational approach to identify targeted therapies.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
1R01AG025392-01
Application #
6863075
Study Section
Special Emphasis Panel (ZAG1-ZIJ-5 (O1))
Program Officer
Finkelstein, Judith A
Project Start
2004-09-30
Project End
2009-07-31
Budget Start
2004-09-30
Budget End
2005-07-31
Support Year
1
Fiscal Year
2004
Total Cost
$295,976
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
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Nordgaard, Curtis L; Karunadharma, Pabalu P; Feng, Xiao et al. (2008) Mitochondrial proteomics of the retinal pigment epithelium at progressive stages of age-related macular degeneration. Invest Ophthalmol Vis Sci 49:2848-55
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Ethen, Cheryl M; Reilly, Cavan; Feng, Xiao et al. (2007) Age-related macular degeneration and retinal protein modification by 4-hydroxy-2-nonenal. Invest Ophthalmol Vis Sci 48:3469-79
Olsen, Timothy W (2007) Treatment of exudative age-related macular degeneration: many factors to consider. Am J Ophthalmol 144:281-3
Decanini, Alejandra; Nordgaard, Curtis L; Feng, Xiao et al. (2007) Changes in select redox proteins of the retinal pigment epithelium in age-related macular degeneration. Am J Ophthalmol 143:607-15
Ethen, Cheryl M; Hussong, Stacy A; Reilly, Cavan et al. (2007) Transformation of the proteasome with age-related macular degeneration. FEBS Lett 581:885-90

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