Age-associated increase in cleaved caspase 3 despite phosphorylation of IGF-1 receptor in the rat retina.

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.