Oxidative Stress and Energetic Failure: Common Features and Dissimilarities in 3 Different Mouse Models of Retinal Pigment Epithelium Phagocytosis Defects.

Amidst the various crucial functions ensured by retinal pigment epithelial (RPE) cells is the circadian phagocytosis of oxidized photoreceptor outer segments (POS) extremities. We have been exploring three mouse models with defective RPE phagocytosis: β5-/- mice inactivated for the αvβ5 integrin synchronizing phagocytosis, MerTKCR knockin mice devoid of the MerTK internalization receptor cleavage site, and Pre-mRNA Processing Factors 31 knockout mice, PRPF splicing factor mutations constituting the second most important cause of autosomic dominant retinitis pigmentosa in patients. Failure in mitochondrial activity and energetic metabolism has been detected in all three models. Signs of cellular stress and increasing oxidative processes were observed in β5-/- and Prpf31+/- RPE cells, while MerTKCR mutants seem to be sensitive to light-derived stress associated with augmented retinal inflammation. Taken together, these results highlight some common pathological mechanisms in these mice, as well as particular features related to the specific function of each protein.