Abstract
Diseases of aging produce many alterations in the retina, but changes in growth factor signaling in normal aging are less characterized. This study investigated modifications in insulin-like growth factor-1 (IGF-1) receptor (IGF-1R) signaling in the retina of Brown Norway x Fischer 344 F1 hybrid rats at 8, 22, and 32 months. Immunoblotting for proteins involved in IGF-1R signal transduction and electroretinograms were done to evaluate changes with aging. Aging produced a significant decrease in b-wave and oscillatory potential amplitudes in the retina. Aging produced increased phosphorylation of IGF-1R. Despite the increase in IGF-1R activity, insulin receptor substrate-1 (IRS-1) phosphorylation was significantly decreased with increasing age. Akt activity was significantly decreased at 22 and 32 months of age, resulting in increased cleaved caspase 3 levels. The results suggest that regulation of IRS-1 phosphorylation may modulate apoptotic rates in the aging retina, potentially preventing activation of vascular endothelial cell growth factor.
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