Nrf‐2 and PGC1‐alpha deletion affects ultrastructural changes in retinal pigmented epithelium associated with the changes of oxidative stress and autophagy markers expression pattern in compound null mice

Abstract

PurposeThere is increasing evidence that NF‐E2‐related factor 2 (Nrf‐2) and peroxisome proliferator‐activated receptor‐gamma coactivator 1‐alpha (PGC‐1α) participate in age‐related retinal degeneration process. Our study aimed to provide de novo, in and ex vivo high‐resolution imaging of eyes from different degenerative mouse models mimicking cellular changes observed in aged retinal pigmented epithelium (RPE).MethodsThe gross morphological alterations of eyes were analyzed by in vivo micro MRI. Oxidative stress marker (4‐HNE) and the autophagy regulators (p62/SQSTM1, Beclin‐1, LC3, Ubiquitin) were examined on thin wax sections by highly specific immunohistochemistry using semi‐quantitative computer aided image analysis. Moreover accurate transmission electron microscopy ultrastructural assay was carried out to monitor the organelle changes in the RPE obtained from Nrf‐2/PGC‐1α knockout mice.ResultsCollectively, age‐related autophagy decline and mitochondrial dysfunction was recorded in the RPE joined with upregulation of stress related biomarkers.ConclusionsTaken together, our experimental data highlight for the first time that common deletion of Nrf‐2 and PGC‐1α might appear to have potential and broad applicability for retinal aging research.