EXPRESSION OF SIRT1 IN CHOROIDAL NEOVASCULAR MEMBRANES

Abstract

In Brief Purpose: 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. Conclusion: 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. SIRT1—a critical regulator of blood vessel formation—was shown to be expressed more frequently in retinal pigment epithelial and endothelial cells in choroidal neovascularization membranes than non–age-related macular degeneration donor eyes. Furthermore, SIRT1 inhibition led to decreased secretion of multiple proangiogenic cytokines from retinal pigment epithelial cells in vitro.