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Norimitsu Ban, Takaaki Inaba, Seiji Miyake, Kazuo Tsubota, Yoko Ozawa; Light-dark Condition Regulates Sirtuin Genes in the Retina. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3417.
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Sirtuins are a family of NAD-dependent deacetylase that are involved in a variety of cellular functions including metabolism, DNA repair, apoptosis, neuronal survival and inflammation. However, much of the sirtuins in the retina are largely unknown. In this study, we analyzed the mRNA levels of seven sirtuins (Sirt1-7) together with the sirtuin-associated molecules, and the effect of light-dark condition on the expression levels in the retina.
Six-week-old male C57BL6/J mice were used. The mice were kept under 12-h light/12-h dark (LD) cycle. After keeping under the usual LD cycle for 2 weeks, the mice were randomly divided into the LD group and constant darkness group (DD group). The DD group was transferred to constant darkness after the dark phase of the last LD cycle, and kept in the dark for two 24-hours DD cycles, and then, sacrificed during third 24-hours DD cycle. The retina and the liver of the LD and DD group mice were sampled every 4 hours, and brain parietal cortex, heart, and kidney of the LD group were also sampled. The mRNA levels of sirtuins, and sirtuin-associated molecules that are Nicotinamide phosphoribosyltransferase (Nampt), peroxisome proliferator-activated receptor gamma coactivator (PGC1α), and transcription factor A, mitochondrial (Tfam), were analyzed by real-time PCR. Nampt is an enzyme for NAD synthesis, and PGC1α and Tfam are related to cellular metabolism.
All seven sirtuins were expressed at high levels in the retina compared with other tissues. Sirtuins showed significant daily variation under the LD condition, with all except Sirt6 being increased during the dark phase. The expression patterns were different under the DD condition, suggesting that sirtuin mRNA levels are affected by light-dark condition. These findings were not obtained in the liver. The expression patterns of Nampt, PGC1α and Tfam in the retina were similar to the patterns of retinal sirtuins.
The gene expression of sirtuins in the retina was at high levels and had unique daily variations depending on light-dark condition. Our observations provide new insights into the metabolic mechanisms of the retina and the sirtuins’ regulatory systems.
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