VEGF-R2/Caveolin-1 Pathway of Undifferentiated ARPE-19 Retina Cells: A Potential Target as Anti-VEGF-A Therapy in Wet AMD by Resvega,an Omega-3/Polyphenol Combination |
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Authors: | Flavie Courtaut,Alessandra Scagliarini,Virginie Aires,Clarisse Cornebise,Jean-Paul Pais de Barros,C line Olmiere,Dominique Delmas |
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Affiliation: | 1.Université de Bourgogne Franche-Comté, 21000 Dijon, France; (F.C.); (A.S.); (V.A.); (C.C.); (J.-P.P.d.B.);2.INSERM Research Center U1231—Cancer and Adaptive Immune Response Team, Bioactive Molecules and Health Research Group, 21000 Dijon, France;3.Lipidomic Analytical Platform, 21000 Dijon, France;4.Laboratoires Thea, 12 Rue Louis-Blériot, 63000 Clermont-Ferrand, France;5.Centre Anticancéreux Georges François Leclerc Center, 21000 Dijon, France |
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Abstract: | Age-related macular degeneration (AMD) is one of the main causes of deterioration in vision in adults aged 55 and older. In spite of therapies, the progression of the disease is often observed without reverse vision quality. In the present study, we explored whether, in undifferentiated ARPE-19 retinal cells, a disruption of the VEGF receptors (VEGF-R)/caveolin-1 (Cav-1)/protein kinases pathway could be a target for counteracting VEGF secretion. We highlight that Resvega®, a combination of omega-3 fatty acids with an antioxidant, resveratrol, inhibits 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. By these pathways, Resvega could present a potential interest as nutritional complementation against AMD. |
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Keywords: | AMD angiogenesis ocular diseases VEGF VEGF-receptor omega-3 fatty acids resveratrol |
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