NAD+/NADH precursor treatment protects against retinal degeneration

Abstract

AbstractPurposeThe retina is highly metabolically active, suggesting that metabolic dysfunction could underlie many retinal degenerative diseases. Nicotinamide adenine dinucleotide (NAD+) is a coenzyme and a co‐substrate in several cellular energetic metabolic pathways. Retinal NAD+ levels decline with age and during retinal damage or degeneration. Maintaining NAD+ levels may be therapeutic in retinal disease. The purpose of this study was to investigate whether systemic treatment with nicotinamide riboside (NR), a NAD+ precursor, is protective in disparate models of retinal damage or degeneration.MethodsFour mouse models of retinal degeneration were tested: a mouse model of light‐induced retinal degeneration, the IRBP knock‐out mouse, rhodopsin‐Tvrm4 mutant mouse, and the rd10 mouse. Mice were IP injected with various concentrations of NR at various times relative to degeneration onset. Retinal function was assessed by ERG, retinal morphology was assessed by OCT and H & E or TUNEL staining, and visual function was assessed by OMR. Retinal NAD+/NADH levels were enzymatically assayed.ResultsEach retinal degeneration model exhibited significantly suppressed retinal and visual function, a severely disrupted photoreceptor cell layer, and significantly decreased numbers of nuclei and increased accumulation of TUNEL‐labeled cells in the outer nuclear layer. These effects were prevented by various NR treatment regimens. Treatment with NR also resulted in increased levels of NAD+ in retina.ConclusionsThis is the first study to report protective effects of NR treatment in models of retinal degeneration and suggests that maintaining retinal NAD+ via systemic NR treatment should be further explored for clinical relevance.