Purpose
Oxidative stress and mitochondrial damage are long protruded cause of detrimental aggregation diseases including age‐related macular degeneration. We recently reported elevated levels of oxidative stress markers, damaged mitochondria, accumulated lipofuscin and drusen like structures in retinal pigment epithelial cells (RPE) of NRF2/PGC1α double knockout mice model.
Methods
Immunostained RPE samples from one‐year old NRF2/PGC1α and age matched wild type mice were used for confocal microscopy analysis.
Results
Lipofuscin accumulation associated with deficiency of mitophagy in RPE cells of NRF2/PGC1α double knockout mice. Immunohistochemical analysis revealed high staining levels of autophagosome marker, microtubule‐associated proteins 1A/1B light chain 3B (LC3B) and mitophagy markers, PTEN‐induced putative kinase 1 (PINK1) and E3 ubiquitin ligase (PARKIN) on damaged mitochondria. Moreover, high levels of late autolysosomal fusion protein Rab7 accumulated in the peri‐nuclear space of RPE cells with increasing incidental colocalization of lipofuscin.
Conclusion
Our study reveals that fusion of lysosomes and autophagosomes occurs, but mitophagy flux is disturbed in lipofuscin loaded RPE cells of NRF2/PGC1α double knockout mice.