The proteasome mediates pathways associated with oxidative stress and inflammation, two pathogenic events correlated with age-related macular degeneration (AMD). In human donor eyes corresponding to four stages of AMD, we found the proteasomal chymotrypsin-like activity increased in neurosensory retina with disease progression. Increased activity correlated with a dramatic increase in the inducible subunits of the immunoproteasome, which was not due to an increase in CD45 positive immune cells in the retina. The novel observation of proteasome transformation may reflect retinal response to local inflammation or oxidative stress with AMD.
Bibliographical noteFunding Information:
The authors thank the Minnesota Lions Eye Bank for their assistance in procuring eyes for this study and Curt Nordgaard for careful review of the manuscript. This work was supported in part by grants from the National Institutes of Health EY014176, EY013623 (DAF) and AG025392 (TWO), a Career Development Award from the American Federation for Aging Research and Foundation Fighting Blindness (DAF), American Health Assistance Foundation, Minnesota Medical Foundation, the University of Minnesota Academic Health Center and Graduate School, the Fesler-Lampert Foundation, and an unrestricted grant to the Department of Ophthalmology from the Research to Prevent Blindness Foundation. CME was supported with a Training Grant for Vision Science (T32-EY07133).
Copyright 2008 Elsevier B.V., All rights reserved.
- 20S Proteasome
- Age-related macular degeneration
- Chymotrypsin-like activity