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Tomoka Ishida, Takeshi Yoshida, Kosei Shinohara, Liu Hongding, Cao KeJia, Kyoko Ohno-Matsui; The role of Sirt1 for regulating VEGF in human RPE. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1512.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal pigment epithelium (RPE) is considered a primary site of producing VEGF for developing choroidal neovascularization (CNV) in age-related macular degeneration (AMD). However, the stimuli regulating VEGF regulation in RPE cells have not been fully clarified. In this study, we examined the role of Sirtuin-1 (Sirt1) on VEGF production in RPE cells and the efficacy of intravitreal Sirt1 activator (Resveratrol: RSV) for the treatment of CNV.<br />
Cultured human RPE cells were incubated in the presence or absence of RSV. And the VEGF gene expression in RPE and protein level in the RPE supernatant were examined by real-time PCR and ELIZA. In vivo study, experimental CNV was induced by laser photocoagulation in C57BL/6 mice and RSV was intravitreally administrated at same time (vehicle: n=12, resveratrol: n=10). After 7 days from laser application, choroidal flat mount and histological analysis were conducted to evaluate of CNV.<br />
The VEGF mRNA and protein expression in human RPE were decreased by RSV at dose dependent manner. The CNV thickness in RSV-treated mice was significantly lower than in vehicle-treated mice by histological analysis. The volume of laser-induced CNV in mice was significantly reduced in the RSV-treated mice as compared to vehicle-treated mice (p=0.03).<br /> <br />
Sirt1 decreased VEGF expression in RPE, and intravitreal administration of RSV suppressed laser-induced CNV formation in mice. Sirt1 may be a new therapeutic option for treatment of AMD.<br /> <br />
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