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

Int J Mol Sci. 2021 Jun 19;22(12):6590. doi: 10.3390/ijms22126590.


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.

Keywords: AMD; VEGF; VEGF-receptor; angiogenesis; ocular diseases; omega-3 fatty acids; resveratrol.

MeSH terms

  • Caveolin 1 / metabolism*
  • Cell Line
  • Drug Evaluation, Preclinical
  • Humans
  • MAP Kinase Signaling System / drug effects
  • Macular Degeneration / prevention & control*
  • Retina / drug effects*
  • Retina / metabolism
  • Transcription Factor AP-1 / antagonists & inhibitors
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism*


  • Caveolin 1
  • Transcription Factor AP-1
  • KDR protein, human
  • Vascular Endothelial Growth Factor Receptor-2