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.