title: NAD(+) maintenance attenuates light induced photoreceptor degeneration.
abstract: 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.
authors.affiliation: Dept. of Ophthalmology and the Neuroscience Center of Excellence, LSU Health Sciences Center, 2020 Gravier Street, Suite D, New Orleans, LA 70112, USA. sbai@lsuhsc.edu
authors.forename: Shi
authors.initials: S
authors.lastname: Bai
authors.forename: Christian T
authors.initials: CT
authors.lastname: Sheline
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D016923:Cell Death; D002478:Cells, Cultured; D002940:Circadian Rhythm; D019610:Cytoprotection; D004195:Disease Models, Animal; D005247:Feeding Behavior; D006861:Hydrogen Peroxide / Q000633:toxicity; D008027:Light / Q000009:adverse effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009243:NAD / Q000378:metabolism*; D009536:Niacinamide / Q000494:pharmacology; D009612:Nicotinamide-Nucleotide Adenylyltransferase / Q000235:genetics / Q000378:metabolism; D016877:Oxidants / Q000633:toxicity; D018384:Oxidative Stress; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D019289:Pyruvic Acid / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012162:Retinal Degeneration / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013997:Time Factors; D015032:Zinc / Q000378:metabolism
chemical_list: D000975:Antioxidants; D016877:Oxidants; D009243:NAD; D009536:Niacinamide; D019289:Pyruvic Acid; D006861:Hydrogen Peroxide; D009612:Nicotinamide-Nucleotide Adenylyltransferase; D015032:Zinc