Endoplasmic reticulum stress proteins are activated in rd retinal degeneration

Objective: To investigate the expression of endoplasmic reticulum (ER) stress proteins in photoreceptor apoptosis in rd mouse (Pde6bRd1/Rd1). Methods: Photoreceptor apoptosis in rd mouse was detected by terminal dUTP transferase nick end labeling (TUNEL). The protein expression of ER stress sensors including glucose-regulated protein-78 (GRP78/BiP), caspase-12, phospho-eukaryotic initiation factor 2α (eIF2α) and phospho-pancreatic ER kinase (PERK) was examined by immunoflurescence and Western Blot analysis. Results: Accompanying photoreceptor apoptosis in rd mouse, protein expression of GRP78/BiP, caspase-12, phospho-eIF2α and phospho-PERK was 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 segment and/or outer nuclear layer (ONL). Conclusion: Activation of ER stress proteins appears to play an important role in rd retinal degeneration. Therefore endoplasmic reticulum stress modulators could be a strong candidate as a therapeutic agent in the treatment of these diseases.