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Yong Lin, Junjie Liu, Li Li, JUxiu Ye, Peter S. Reinach, Jia Qu, Dongsheng Yan; Endothelial-specific SIRT1 Deletion Inhibits Retinal Vascular Endothelial Cell Migration. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3655.
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© ARVO (1962-2015); The Authors (2016-present)
SIRT1 is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase, abundantly expressed in vascular endothelial cells and has an essential role in angiogenesis. However, its contribution to retinal vascular development remains unclear. Here we characterize its involvement in regulating this process during both physiological and pathological retinal vascular development.
Endothelial-specific SIRT1 deletion mice were established using the Cre-loxP system. Vascular endothelial cells (EC) were isolated using magnetic beads coated with anti- CD31 antibody. SIRT1 expression was detected by immunostaining and Western blotting. Retinal whole-mount staining analyzed the retinal vascular pattern and vessel obliteration during development as well as in an oxygen-induced retinopathy (OIR) mouse model. In vitro, SIRT1 was knocked down in cultured retinal ECs using small interfering RNA (siRNA). Transwell and matrigel angiogenesis assays evaluated the role of SIRT1 in modulating cell migration and tube formation, respectively.
In EC specific SIRT1 conditional knockout (SIRT1 cKO) mice, their retinal vascularized area size was dramatically smaller than that in control mice (SIRT1 flox/flox) at P5 and P8. In OIR mice model, SIRT1 ablation in ECs suppressed retinal revascularization markedly and consequently increased retinal avascularity compared to that in the control mice. SIRT1 down-regulation in human retinal microvascular endothelial cells inhibited cell migration and tube formation.
SIRT1 contributes to both physiological and pathological retinal neovascularization through promoting retinal EC migration. SIRT1 may be a potential drug target to treat retinal diseases in which there is inappropriate vascularization leading to compromise of visual function and even blindness.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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