NAD(+) maintenance attenuates light induced photoreceptor degeneration.
NAD(+) maintenance attenuates light induced photoreceptor degeneration.
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DOI：
10.1016/j.exer.2012.12.007
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发表时间：
2013-03
影响因子：
3.4
通讯作者：
Sheline, Christian T.
中科院分区：
文献类型：
--
作者：
Bai, Shi;Sheline, Christian T.
光诱导的视网膜损伤（LD）发生在手术或阳光照射后。我们以前表明，锌（Zn 2+）积累在光感受器和RPE细胞LD后，但在细胞死亡之前，丙酮酸或烟酰胺衰减可能通过恢复烟酰胺腺嘌呤二核苷酸（NAD+）的水平所产生的死亡。我们首先使用原代视网膜培养物检查了NAD+的水平和丙酮酸盐或烟酰胺在氧化毒性中的功效。我们接下来在体内操纵NAD+水平并测试LD对光感受器和RPE的影响。NAD+水平在哺乳动物中以24小时的节奏循环，这受到进食时间表的影响。因此，我们通过给予烟酰胺、颠倒喂养时间表或使用过表达细胞质烟酰胺单核苷酸腺苷转移酶-1（cytNMNAT 1）（一种NAD+合成酶）的转基因小鼠来测试增加NAD+水平对LD的影响。还在培养物和视网膜切片中评估了Zn 2+积累。通过OCT和塑料切片检查光损伤动物的视网膜，并测量视网膜NAD水平。与夜间喂食的大鼠或未处理的大鼠相比，白天喂食或烟酰胺处理的大鼠显示出更少的NAD+损失和LD，而不改变Zn 2+染色模式。CytNMNAT 1在LD后显示较少的Zn 2+染色、NAD+损失和细胞死亡。总之，强光，Zn 2+和氧化毒性引起的Zn 2+，NAD+的损失，和细胞死亡的增加，这是衰减NAD+恢复。因此，NAD+水平在LD诱导的光感受器和RPE细胞死亡中起保护作用。
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.
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影响因子：
5.5
作者：
Duan, Yuntao;Gross, Robert A.;Sheu, Shey-Shing
通讯作者：
Sheu, Shey-Shing
影响因子：
4.2
作者：
KUHN, F;MORRIS, R;MASSEY, M
通讯作者：
MASSEY, M
影响因子：
17.8
作者：
Organisciak, Daniel T.;Vaughan, Dana K.
通讯作者：
Vaughan, Dana K.
影响因子：
4.8
作者：
Lin, SS;Manchester, JK;Gordon, JI
通讯作者：
Gordon, JI
DOI：
10.1097/iae.0b013e3181b0da88
发表时间：
2009-10-01
影响因子：
3.3
作者：
Jain, Atul;Desai, Rajen U.;Sarraf, David
通讯作者：
Sarraf, David