Silberman Dafne M, Ross Kenneth, Sande Pablo H, Kubota Shunsuke, Ramaswamy Sridhar, Apte Rajendra S, Mostoslavsky Raul
Laboratory of Retinal Neurochemistry and Experimental Ophthalmology, Department of Human Biochemistry, School of Medicine, CEFyBO-CONICET-UBA, Buenos Aires, Argentina; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, United States of America.
Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, United States of America.
PLoS One. 2014 Jun 4;9(6):e98831. doi: 10.1371/journal.pone.0098831. eCollection 2014.
The retina is one of the major energy consuming tissues within the body. In this context, synaptic transmission between light-excited rod and cone photoreceptors and downstream ON-bipolar neurons is a highly demanding energy consuming process. Sirtuin 6 (SIRT6), a NAD-dependent deacylase, plays a key role in regulating glucose metabolism. In this study, we demonstrate that SIRT6 is highly expressed in the retina, controlling levels of histone H3K9 and H3K56 acetylation. Notably, despite apparent normal histology, SIRT6 deficiency caused major retinal transmission defects concomitant to changes in expression of glycolytic genes and glutamate receptors, as well as elevated levels of apoptosis in inner retina cells. Our results identify SIRT6 as a critical modulator of retinal function, likely through its effects on chromatin.
视网膜是体内主要的能量消耗组织之一。在此背景下，光激发的视杆和视锥光感受器与下游ON双极神经元之间的突触传递是一个对能量消耗要求很高的过程。沉默调节蛋白6（SIRT6）是一种依赖烟酰胺腺嘌呤二核苷酸（NAD）的去乙酰化酶，在调节葡萄糖代谢中起关键作用。在本研究中，我们证明SIRT6在视网膜中高表达，控制组蛋白H3K9和H3K56的乙酰化水平。值得注意的是，尽管组织学表现明显正常，但SIRT6缺乏导致主要的视网膜传递缺陷，同时伴随着糖酵解基因和谷氨酸受体表达的变化，以及视网膜内层细胞凋亡水平的升高。我们的结果表明SIRT6可能通过其对染色质的作用，是视网膜功能的关键调节因子。
