More recently, studies have shown that polyphenols could also prevent or improve vision in patients with ocular diseases and especially Age-related macular degeneration (AMD) which is an eye disease characterized by damage to the central part of the retina, the macula, and that affects millions of people worldwide. Despite therapeutic advances thanks to the use of anti-vascular endothelial growth factor (VEGF), many resistance mechanisms have been found to accentuate the visual deficit. In the present study, we explored whether a nutraceutical supplementation based on mediterranean diet associating polyphenols from red wine and omega-3 fatty acids was able to counteract laser-induced choroidal neovascularization (CNV) in mice and moleular mechanism involved in neaovasculariation of AMD. We highlight that nutraceutical formulation, Resvega®, composed of DHA/EPA and resveratrol, significantly reduced CNV in mice and a proteomic approach confirmed that Resvega® could counteract the progression of AMD through a pleiotropic effect targeting key regulators of neoangiogenesis in retina cells in vivo. These events were associated with an accumulation of resveratrol metabolites within the retina. A molecular analysis revealed that Resvega®, inhibited VEGF-A secretion in vitro by disrupting the dissociation of the VEGF-R2/Cav-1 complex into rafts and subsequently preventing MAPK activation. Moreover, DNA ChIP analysis reveals that this combination prevents the interaction between AP-1 and vegf-a and vegf-r2 gene promoters. Therefore, a supplementation of omega-3/resveratrol could improve the management or slow the progression of AMD in patients with this condition.
This work was supported by grants from the ANRT N°2016/0003, by a French Government grant managed by the French National Research Agency under the program “Investissements d’Avenir”, reference ANR-11-LABX-0021, the Conseil Régional Bourgogne, Franche-Comte (PARI grant) and the FEDER (European Funding for Regional Economic Development).
Presenting author: Dominique Delmas – Inserm Research Center U1231, University of Bourgogne
Additionnal authors: Flavie Courtaut | Inserm Research Center U1231, University of Bourgogne, Virginie Aires | Inserm Research Center U1231, University of Bourgogne, Niyazi Acar | Eye and Nutrition Research Group, Centre des Sciences du Goût et de l’Alimentation, AgroSup Dijon, Lionel Bretillon | Eye and Nutrition Research Group, Centre des Sciences du Goût et de l’Alimentation, AgroSup Dijon, Alessandra Scagliarini | Inserm Research Center U1231, University of Bourgogne, Clarisse Cornebise | Inserm Research Center U1231, University of Bourgogne, Ida Chiara Guerrera | Proteomics Platform Necker, Université de Paris, Cerina Chhuon | Proteomics Platform Necker, Université de Paris, Jean-Paul Pais de Barros | Lipidomic Analytical Platform, 21000 Dijon, Céline Olmiere | Laboratoires Thea, 12 Rue Louis-Blériot, 63000 Clermont-Ferrand
Keywords: Resveratrol, fatty acids, mediterranean supplementation, ocular disease