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Shunsuke Kubota, Yoko Ozawa, Toshihide Kurihara, Mariko Sasaki, Kenya Yuki, Seiji Miyake, Kousuke Noda, Susumu Ishida, Kazuo Tsubota; Resveratrol Attenuates Diabetes-Induced Retinal Inflammation by Regulating an AMP-Activated Protein Kinase/Nuclear Factor-B Axis. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5946.
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© ARVO (1962-2015); The Authors (2016-present)
Recently, the polyphenolic phytoalexin resveratrol has been shown to exert various bioactivities in addition to its classical antioxidant property. The aim of the present study was to investigate whether resveratrol attenuates diabetes-induced retinal inflammation through the regulation of AMP-activated protein kinase (AMPK) activity.
C57BL/6 mice with streptozotocin-induced diabetes were treated with resveratrol orally at the dose of 50 mg/kg for 7 days or with the AMPK activator 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) intraperitoneally at the dose of 100 mg/kg 24 hours before sacrifice. Leukocyte adhesion to the retinal vasculature was examined with a concanavalin A lectin perfusion-labeling technique. Retinal protein levels of intercellular adhesion molecule (ICAM)-1,vascular endothelial growth factor (VEGF), and phosphorylated AMPK and nuclear factor(NF)-ΚBp65 were evaluated by enzyme-linked immunosorbent assay or western blotting. Retinal activity of sirtuin (SIRT) 1 was measured by deacetylase fluorometric assay.
Administration of resveratrol to diabetic mice significantly reduced diabetes-induced retinal leukocyte adhesion together with retinal expression of ICAM-1 and VEGF. Importantly, either resveratrol or AICAR significantly reversed AMPK dephosphorylation and NF-ΚB phosphorylation, both of which were induced in the diabetic retina. In parallel, retinal SIRT1 activity, reduced in diabetic animals, was significantly augmented by treatment with resveratrol.
Resveratrol suppressed cellular and molecular inflammatory responses by normalizing diabetes-induced downregulation of AMPK and subsequent activation of the NF-ΚB signaling pathway. Our data suggest the potential use of resveratrol as a therapeutic agent for diabetic retinopathy.
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