Role of Nuclear NAD⁺ in Retinal Homeostasis

The retina is one of the most metabolically active tissues and maintenance of metabolic homeostasis is critical for retinal function. Nicotinamide adenine dinucleotide (NAD⁺) is a cofactor that is required for key processes, including the electron transport chain, glycolysis, fatty acid oxidation, and redox reactions. NAD⁺ also acts as a co-substrate for enzymes involved in maintaining genomic DNA integrity and cellular homeostasis, including poly-ADP ribose polymerases (PARPs) and Sirtuins. This review highlights the importance of NAD⁺ in the retina, including the role of enzymes involved in NAD⁺ production in the retina and how NAD⁺-consuming enzymes may play a role in disease pathology. We also suggest a cell death pathway that may be common in multiple models of photoreceptor degeneration and highlight the role that NAD⁺ likely plays in this process. Finally, we explore future experimental approaches to enhance our understanding of the role of NAD⁺ in the retina.