NAD(+) maintenance attenuates light induced photoreceptor degeneration.

Light-induced retinal damage (LD) occurs after surgery or sun exposure. We previously showed that zinc (Zn(2+)) accumulated in photoreceptors and RPE cells after LD but prior to cell death, and pyruvate or nicotinamide attenuated the resultant death perhaps by restoring nicotinamide adenine dinucleotide (NAD(+)) levels. We first examined the levels of NAD(+) and the efficacy of pyruvate or nicotinamide in oxidative toxicities using primary retinal cultures. We next manipulated NAD(+) levels in vivo and tested the affect on LD to photoreceptors and RPE. NAD(+) levels cycle with a 24-h rhythm in mammals, which is affected by the feeding schedule. Therefore, we tested the affect of increasing NAD(+) levels on LD by giving nicotinamide, inverting the feeding schedule, or using transgenic mice which overexpress cytoplasmic nicotinamide mononucleotide adenyl-transferase-1 (cytNMNAT1), an NAD(+) synthetic enzyme. Zn(2+) accumulation was also assessed in culture and in retinal sections. Retinas of light damaged animals were examined by OCT and plastic sectioning, and retinal NAD(+) levels were measured. Day fed, or nicotinamide treated rats showed less NAD(+) loss, and LD compared to night fed rats or untreated rats without changing the Zn(2+) staining pattern. CytNMNAT1 showed less Zn(2+) staining, NAD(+) loss, and cell death after LD. In conclusion, intense light, Zn(2+) and oxidative toxicities caused an increase in Zn(2+), NAD(+) loss, and cell death which were attenuated by NAD(+) restoration. Therefore, NAD(+) levels play a protective role in LD-induced death of photoreceptors and RPE cells.