Resvega, a Nutraceutical Preparation, Affects NFκB Pathway and Prolongs the Anti-VEGF Effect of Bevacizumab in Undifferentiated ARPE-19 Retina Cells

Age-related macular degeneration (AMD) is an irreversible chronic degenerative pathology that affects the retina. Despite therapeutic advances thanks to the use of anti-vascular endothelial growth factor (VEGF) agents, resistance mechanisms have been found to accentuate the visual deficit. In the present study, we explored whether a nutraceutical formulation composed of omega-3 fatty acids and resveratrol, called Resvega (R), was able to disrupt VEGF-A secretion in human ARPE-19 retina cells. We found that Resvega (R) inhibits VEGF-A secretion through decreases in both the PI3K-AKT-mTOR and NF kappa B signaling pathways. In NF kappa B signaling pathways, Resvega (R) inhibits the phosphorylation of the inhibitor of NF kappa B, I kappa B, which can bind NF kappa B dimers and sequester them in the cytoplasm. Thus, the NF kappa B subunits cannot migrate to the nucleus where they normally bind and stimulate the transcription of target genes such as VEGF-A. The I kappa B kinase complex (IKK) is also affected by Resvega (R) since the nutraceutical formulation decreases both IKK alpha and IKK beta subunits and the IKK gamma subunit which is required for the stimulation of IKK. Very interestingly, we highlight that Resvega (R) could prolong the anti-angiogenic effect of Avastin (R), which is an anti-VEGF agent typically used in clinical practice. Our results suggest that Resvega (R) may have potential interest as nutritional supplementation against AMD.