We undertook this study to characterize SIRT6 in the mouse retina. We found that SIRT6 is expressed and is active in the mouse retina. SIRT6 deficiency has no effect on retinal structure but KO mice retinas exhibited up-regulation of the glucose transporter GLUT1 and down-regulation of the metabotropic glutamate Ginsenoside-Ro receptor Grm6, indicating that both neurotransmission and glucose levels in the retina might be regulated by SIRT6. ERG analysis showed that the retina of SIRT6-KO mice was profoundly impaired. The retina is one of the major energy consuming tissues within the body, maintaining high glucose metabolism for its energetic needs. Moreover, synaptic transmission is a highly energy demanding process, therefore the retina evolved mechanisms to coordinate synaptic activity with glucose homeostasis. SIRT6 is a member of the sirtuin family of NAD-dependent deacylases that acts to maintain homeostatic control of glucose metabolism by repressing a number of enzymes involved in this process. Although SIRT6 plays a critical role in modulating bioenergy homeostasis and that metabolic control is essential for vision, very little is known regarding this enzyme’s involvement in retinal physiology. In this study, we aimed for the first functional characterization of SIRT6 in the mouse retina. Recent studies have shown that SIRT6 is expressed in the mouse retina and its levels seem to be higher in this tissue compared to brain, heart, liver or kidney. We confirmed the presence of SIRT6 in the mouse retina and were able to determine that it is expressed in all retinal layers. Moreover, SIRT6 was found to be active in the retina since lack of this enzyme resulted in significantly increased level of acetylation of 
two of its described substrates, H3K9 and H3K56, in KO retinas compared to WT. Our previous studies demonstrated that SIRT6 deficiency in mice renders a phenotype characterized by a profound hypoglycemiadue to increased glucose uptake. Molecularly, SIRT6 deacetylates H3K9 and H3K56, repressing expression of glycolytic genes, including the glucose transporter GLUT1. In the absence of SIRT6, those genes are up-regulated, causing uncontrolled glucose uptake and a switch towards glycolytic metabolism. Since GLUT1 is the sole transporter responsible for the transport of glucose across the blood�Cretinal barrier, we focused on this transporter. Indeed, we found that mRNA and protein levels of GLUT1 were significantly increased in retinas from SIRT6 KO mice, suggesting a glucose imbalance in this tissue. It is expected that GLUT1 upregulation would be accompanied by an increase of glucose availability in the retina making difficult to explain the defects we observed. On the other hand, upregulation of GLUT1 could as well indicate a compensatory mechanism due to local low levels of glucose since, as we published, blood glucose is being mostly uptake by skeletal muscle and adipose tissue in SIRT6 deficient mice. Whether such chromatin-dependent changes in GLUT1 play a causal role in the functional defects we observed in the SIRT6 KO retinas remains to be determined. Glutamate is the major excitatory neurotransmitter in the central nervous Forsythin system, and plays important roles in regulating cell excitability and synaptic transmission. Multiple molecular events are coordinated during synaptic activation, including sodium pump activity, receptor trafficking, cytoskeletal rearrangements, signaling, and metabolic processes, making synaptic activity an energetically costly process.