We have optimized a method to directly measure oxygen consumption in acutely isolated, ex vivo mouse retina and demonstrate that photoreceptors have low mitochondrial reserve capacity. Our data provide a plausible explanation for the high vulnerability of photoreceptors to altered energy homeostasis caused by mutations or metabolic challenges.

Highlights d WGBS identifies 2,054 differentially methylated regions (DMRs) in aging mouse rods d DMRs are present in regulatory regions and cluster at chromosomal hotspots d DMRs are linked to dysregulation of aging pathways and energy metabolism d Old retinas exhibit lower basal respiration and higher fatty acid dependency