Rpe, short for Retinal Pigment Epithelium, consists of specialized, multifunctional cells in the retina forming a monolayer adjoining photoreceptor cells. It is a critical component of the blood-retinal barrier, playing essential roles in maintaining retinal homeostasis, supporting photoreceptor health, and participating in the metabolic symbiosis with photoreceptors [2,3]. The RPE takes up glucose from circulation and passes it to photoreceptors, while photoreceptors produce energy substrates for the RPE. Additionally, RPE phagocytoses "used" photoreceptor outer segments to mitigate light-induced damage [2].

In a study where the gene encoding the mitochondrial antioxidant enzyme, manganese superoxide dismutase (Sod2), was conditionally deleted in the RPE of albino BALB/cJ mice (a form of gene knockout), Sod2 knockout (KO) mice showed reduced RPE function with age, increased oxidative stress, and alterations in RPE morphology and mitochondrial structure and function. This was also associated with a compensatory increase in RPE glycolytic metabolism and severe disruption of photoreceptor mitochondria, demonstrating that mitochondrial oxidative stress in RPE can lead to RPE dysfunction and metabolic reprogramming, and secondary metabolic stress in photoreceptors, suggesting a mechanism of retinal degeneration in dry AMD [1].

In conclusion, Rpe is vital for maintaining the metabolic ecosystem in the retina and the health of photoreceptors. The use of gene knockout mouse models, such as the Sod2 KO in RPE, has revealed its role in retinal degeneration associated with age-related macular degeneration, providing insights into the underlying mechanisms and potential therapeutic targets for this disease.