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C.M. Ethen, A. Decanini, X. Feng, T.W. Olsen, D.A. Ferrington; Altered Retinal Proteasome Function With Progression of Age–Related Macular Degeneration . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4879.
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The proteasome mediates processes essential for cell viability, such as cell cycle regulation, signal transduction and protein quality control. In several neurodegenerative diseases, a loss in proteasome function correlates with disease onset, suggesting a potential role for proteasome in the disease process. This study investigated how proteasome function is altered at progressive stages of age–related macular degeneration (AMD).
Human donor eyes obtained from the Minnnesota Lions Eye Bank were graded for AMD stage using the Minnesota Grading System (MGS, Olsen and Feng, 2004, IOVS 45: 4484–90). Proteasome activity was measured using fluorogenic peptides in separate preparations of the neurosensory retina and retinal pigment epithelium (RPE) at four progressive stages of AMD. Western immunoblotting was performed using antibodies that recognize specific proteasomal subunits to measure proteasome content.
In the neurosensory retina, there was a significant increase in proteasome activity at late stages (MGS3 & MGS4) of AMD that was not due to an increase in proteasome content. In contrast, there was a three–fold increase in total proteasome content in RPE at late stages of AMD, but no corresponding change in proteasome activity.
Proteasome appears to be altered at late stages of the disease, implicating a role for this protease in AMD progression. In addition, we observed tissue–specific changes occurring in both proteasome content and activity within the retina.
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