RPE of Aged Mice Displays TLR3 Activation and dsRNA Binding Protein Reduction

Abstract

Purpose: : We previously showed that long double stranded RNAs (dsRNAs) activate toll-like receptor-3 (TLR3) (Kleinman et al. Nature 2008) and induce retinal degeneration in mice (Yang et al. NEJM 2008). Here we studied the expression of dsRNA binding protein 2 (DSRBP2) and TLR3 phosphorylation in the human and mice eyes.

Methods: : RNA and protein levels of DSRBP2 were assessed by real-time RT-PCR and Western blotting/immunohistochemistry in human eyes and in young (3-month-old) and aged (30-36-month-old) C57Bl/6 mice. TLR3 phosphorylation was assessed by immunoblotting in young and aged mice.

Results: : DSRBP2 was highly expressed in the human retina and retinal pigmented epithelium (RPE), with higher levels in the macular compared to peripheral regions. In mice eyes, there was a dramatic reduction of DSRBP2 expression and increase in TLR3 phosphorylation in the RPE of aged compared to young mice. DSRBP2 expression levels in the retina and cornea were not significantly different between aged and young mice.

Conclusions: : These data suggest a specific dysregulation of dsRNA processing in senescent RPE that might have implications for retinal degenerations.

Keywords: age-related macular degeneration • aging • retinal pigment epithelium