NAD+ inhibits the metabolic reprogramming of RPE cells in early AMD by upregulating mitophagy

Abstract

Age-related macular degeneration (AMD) is a leading cause of blindness and is becoming a global crisis, with the number of affected people expected to reach 288 million by 2040 worldwide. Retinal pigment epithelium (RPE) performs a number of highly diverse functions that are essential to maintaining the normal health and function of the retina. Alterations to retinal metabolism and remodeling are an early feature of AMD. The pathology of AMD is associated with mitochondrial dysfunction. Mitophagy is vital to promote a metabolic shift towards glycolysis that is required for cell differentiation. Nicotinamide adenine dinucleotide (NAD+) acts as a central metabolic cofactor, plays a pivotal role in regulating cellular metabolism and energy homeostasis, and may aid disease treatment. Therefore, we hypothesized that NAD+ may restore homeostasis by inducing mitophagy in AMD, thereby reducing the damage caused by metabolic reprogramming. Since NAD+ has shown promise as a novel and inexpensive cytoprotective agent in the treatment of oxidative stress-related disease, patients with AMD may benefit from NAD+ treatment.