Death of photoreceptors in organotypic retinal explant cultures: Implication of rhodopsin accumulation and endoplasmic reticulum stress

Here we suggest that endoplasmic reticulum (ER)-stress may be induced following aberrant rhodopsin accumulation in photoreceptors in explanted rat retinas. Rhodopsin accumulation was accompanied by increased phosphorylation of pancreatic ER-kinase and eukaryotic initiator factor 2α as well as increased levels of C/EBP homologous protein, glucose-regulated protein 78 and eventually increased cleaved caspase-12 and cleaved caspase-3. Glucose-regulated protein 78, pancreatic ER-kinase, caspase-12 and cleaved caspase-3 were present in photoreceptors, indicating that ER-stress and apoptosis are induced in this cell population. These results suggest that ER-stress and subsequent apoptosis is induced in healthy photoreceptors, presumably by aberrant accumulation of rhodopsin and the phosphorylation of eukaryotic initiator factor 2α. The explant culture system may allow investigations of neuroprotective strategies.

Research highlights► This study focuses on mislocalized and accumulated rhodopsin in photoreceptors and the expression of ER-stress proteins. ► We have used retinal explant cultures for increased rhodopsin accumulation and analyzed the induction of ER-stress using light and confocal microscopy, as well as immunohistochemistry and Western blot. ► Although some studies on ER-stress and photoreceptor apoptosis have been published elsewhere our study contains several novel findings. For example, we show that the appearance of ER-stress sensors coincides with the accumulation of rhodopsin in injured photoreceptors. The study suggests that not only caspase-3 but also caspase-12 contributes to photoreceptor apoptosis in vitro.