The above described study also reported that the levels of PINK1 and NRF2 decreased in dysmorphic perifoveal RPE of early AMD eyes, suggesting that the two cytoprotective mechanisms, PINK1-mediated mitophagy and NRF2-dependent antioxidant defense, are weakened in AMD and likely contribute to the observed RPE heterogeneity (Wang et al, 2014; Datta et al, 2023). This evidence concerns the gene NFE2L2 and age-related macular degeneration.