Activation of endoplasmic reticulum stress proteins in light-induced retinal degeneration

OBJECTIVE: To investigate the expression of endoplasmic reticulum stress proteins in photoreceptor apoptosis in light-induced retinal degeneration. METHODS: Exposure to excessive levels of light induced photoreceptor apoptosis and had been previously used as a model for the study of retinal degeneration. Photoreceptor apoptosis was detected by terminal dUTP transferase nick end labeling (TUNEL). The protein expression levels of ER stress sensors including glucosejregulated protein-78 (GRP78/BiP), caspase-12, phospho-eukaryotic initiation factor 2alpha (eIF2alpha) and phospho- double-stranded RNA-activated protein kinase-like endoplasmic reticulum kinase (PERK) were examined by immunojfluorescence and Western blot analysis. RESULTS: Following light exposure, the protein expression levels of GRP78/BiP, caspase-12, phospho-eIF2alpha and phospho-PERK were up-regulated in a time dependent manner. The up-regulation of these proteins coincided with or preceded the photoreceptor apoptosis. At the peak of their expression, they were mainly located in the photoreceptor inner segments and/or outer nuclear layers (ONL). CONCLUSION: Activation of endoplasmic reticulum stress proteins appears to play an important role in light-induced retinal degeneration. Therefore endoplasmic reticulum stress modulators could become a strong candidate for a therapeutic agent in treatment of these diseases.