title: SIRT6 is required for normal retinal function.
abstract: 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.
authors.affiliation: 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.
authors.forename: Dafne M
authors.initials: DM
authors.lastname: Silberman
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Ross
authors.affiliation: Laboratory of Retinal Neurochemistry and Experimental Ophthalmology, Department of Human Biochemistry, School of Medicine, CEFyBO-CONICET-UBA, Buenos Aires, Argentina.
authors.forename: Pablo H
authors.initials: PH
authors.lastname: Sande
authors.affiliation: Department of Ophthalmology and Visual Sciences and Developmental Biology, Washington University, St Louis, Missouri, United States of America.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Kubota
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Sridhar
authors.initials: S
authors.lastname: Ramaswamy
authors.affiliation: Department of Ophthalmology and Visual Sciences and Developmental Biology, Washington University, St Louis, Missouri, United States of America.
authors.forename: Rajendra S
authors.initials: RS
authors.lastname: Apte
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Raul
authors.initials: R
authors.lastname: Mostoslavsky
mesh_terms: D000107:Acetylation; D000818:Animals; D016000:Cluster Analysis; D015870:Gene Expression; D020869:Gene Expression Profiling; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017470:Receptors, Glutamate / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000502:physiology*; D037761:Sirtuins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D051272:Glucose Transporter Type 1; D006657:Histones; D012333:RNA, Messenger; D017470:Receptors, Glutamate; C501860:Sirt6 protein, mouse; D037761:Sirtuins