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C. Nordgaard, P. P. Karunadharma, X. Feng, T. W. Olsen, D. A. Ferrington; Mitochondrial Proteomics of the Retinal Pigment Epithelium in Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2191.
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Age-related macular degeneration (AMD) is a major cause of blindness among older adults in developed nations. While treatments for exudative AMD are becoming increasingly effective, no proven treatments exist for atrophic AMD and prophylactic options for both forms of the disease are limited. The development of new prevention and treatment strategies require elaboration of the biochemical pathways underlying AMD pathophysiology. To this end, we previously analyzed retinal pigment epithelium (RPE) lysates using a proteomic approach and found AMD-related changes in the content of several mitochondrial proteins. This study narrows the focus of our proteomic analysis to the mitochondrial sub-proteome.
The RPE was dissected from human donor globes categorized into one of four progressive stages of AMD using the Minnesota Grading System. Differential centrifugation was used to obtain a mitochondria-enriched fraction from RPE lysates, as verified by organelle-specific Western blotting. Proteins were resolved using two-dimensional gel electrophoresis followed by silver staining, and identified by mass spectrometry.
Mitochondrial yield and purification were generally consistent across the four MGS stages. Of 220 spots analyzed, the density of more than 20 changed significantly with respect to MGS stage. The identified proteins mitigate mitochondrial structure and functions such as oxidative phosphorylation, mitochondrial translation, and mitochondrial apoptotic signaling.
We identified several unique proteins that have not been previously associated with AMD. These findings implicate mitochondrial dysfunction in the onset and progression of AMD. Further studies to delineate pathological changes in mitochondria will likely improve our understanding of AMD disease processes.
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