title: Expression of SIRT1 in choroidal neovascular membranes.
abstract: OBJECTIVE
  SIRT1 is a deacetylase that has been shown to be instrumental in embryonic and pathologic vascular formation. The purpose of this study was to evaluate the potential role of SIRT1 in the pathogenesis of choroidal neovascularization in age-related macular degeneration.
  
  
  METHODS
  The expression of SIRT1 was assessed via immunohistochemistry in nine excised human choroidal neovascularization membranes and seven non-age-related macular degeneration donor eyes. Enzyme-linked immunosorbent assay-based angiogenesis arrays were used to assess the potential of an SIRT1 inhibitor, nicotinamide, to reduce secretion of 10 unique proangiogenic cytokines from retinal pigment epithelial cells.
  
  
  RESULTS
  SIRT1 was expressed more frequently in choroidal neovascularization membranes than donor eyes about vascular endothelial cells (78 vs. 29% positive cases) and retinal pigment epithelial cells (57 vs. 14% positive cases). SIRT1 inhibition in retinal pigment epithelial cells correlated with significantly decreased secretion of three potent proangiogenic cytokines: angiogenin, platelet-derived growth factor BB, and vascular endothelial growth factor A.
  
  
  CONCLUSIONS
  SIRT1 levels appear elevated in human choroidal neovascularization membranes compared with control eyes. Moreover, inhibition of SIRT1 activity is correlated with decreased secretion of potent proangiogenic cytokines. Collectively, these data support a potential role for SIRT1 in the pathogenesis of neovascular age-related macular degeneration.
authors.affiliation: Department of Ophthalmology, Henry C. Witelson Ocular Pathology Laboratory, McGill University, Montreal, Canada. shawn.maloney@mail.mcgill.ca
authors.forename: Shawn C
authors.initials: SC
authors.lastname: Maloney
authors.forename: Emilia
authors.initials: E
authors.lastname: Antecka
authors.forename: Tamara
authors.initials: T
authors.lastname: Granner
authors.forename: Bruno
authors.initials: B
authors.lastname: Fernandes
authors.forename: Li-Anne
authors.initials: LA
authors.lastname: Lim
authors.forename: Maria E
authors.initials: ME
authors.lastname: Orellana
authors.forename: Miguel N
authors.initials: MN
authors.lastname: Burnier
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D020256:Choroidal Neovascularization / Q000201:enzymology*; D016207:Cytokines / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000494:pharmacology; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000201:enzymology; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014019:Tissue Donors; D014803:Vitamin B Complex / Q000494:pharmacology; D057135:Wet Macular Degeneration / Q000201:enzymology*
chemical_list: D016207:Cytokines; D014803:Vitamin B Complex; D009536:Niacinamide; C447939:SIRT1 protein, human; D056564:Sirtuin 1