کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
4011318 | 1602614 | 2013 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: NAD+ maintenance attenuates light induced photoreceptor degeneration NAD+ maintenance attenuates light induced photoreceptor degeneration](/preview/png/4011318.png)
Light-induced retinal damage (LD) occurs after surgery or sun exposure. We previously showed that zinc (Zn2+) 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. Zn2+ 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 Zn2+ staining pattern. CytNMNAT1 showed less Zn2+ staining, NAD+ loss, and cell death after LD. In conclusion, intense light, Zn2+ and oxidative toxicities caused an increase in Zn2+, 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.
► H2O2 increases Zn2+, decreases NAD+, and kills primary retinal cultures (PRC).
► Pyruvate, nicotinamide (N) and NAD+ restore NAD+ levels and reduce PRC death.
► Retinal NAD+ levels are reduced by light damage (LD), and N restores NAD+ levels.
► LD and NAD+ loss were attenuated by only feeding during the day.
► Overexpressing NMNAT1 attenuates Zn2+ staining, NAD+ loss, and light damage.
Journal: Experimental Eye Research - Volume 108, March 2013, Pages 76–83