Resveratrol inhibits pathological retinal neovascularization in a mouse model of macular teleangiectasia. - GreenMedInfo Summary
Resveratrol inhibits pathologic retinal neovascularization in Vldlr(-/-) mice.
Invest Ophthalmol Vis Sci. 2011 Jan 31. Epub 2011 Jan 31. PMID: 21282584
Department of Ophthalmology, Harvard Medical School, Children's Hospital Boston, USA;
Purpose: Macular telangiectasia (MacTel) is a vision-threatening retinal disease with unknown pathogenesis and no approved treatment. Very low density lipoprotein receptor mutant mice (Vldlr-/-) exhibit critical features of MacTel such as retinal neovascularization and photoreceptor degeneration. In this study, we evaluate the therapeutic potential of resveratrol, a plant polyphenol, in Vldlr-/- mice as a model for MacTel. Methods: Vldlr(-/-) and wild type mice at P21-60 or P10-30 of age were treated orally with resveratrol. The number of neovascular lesions was evaluated on retinal flatmounts and resveratrol effects on endothelial cells were assessed by Western Blot for phosphorylated ERK1/2, aortic ring and migration assays. Vegf and Gfap expression was evaluated in laser-capture microdissected retinal layers of angiogenic lesions and non-lesion areas from Vldlr-/- and wild type retinas. Results: Vldlr-/- retinas develop vascular lesions from P15 onwards, associated with local upregulation of VEGF in photereceptors, and Gfap in the inner retina. Oral resveratrol reduces lesion formation when administered either before or after disease onset. The reduction of vascular lesions in resveratrol-treated Vldlr-/- mice is associated with suppression of retinal VEGF transcription. Resveratrol also reduces endothelial ERK1/2 signaling as well as migration and proliferation of endothelial cells. Furthermore, a trend towards increased rhodopsin mRNA in Vldlr-/- retinas is observed. Conclusions: Oral administration of resveratrol is protective against retinal neovascular lesions in Vldlr-/- mice by inhibiting VEGF expression and angiogenic activation of retinal endothelial cells. These results suggest that resveratrol might be a potentially safe and effective intervention for treating patients with MacTel.