Red wine extract and resveratrol from grapevines could counteract AMD by inhibiting angiogenesis promoted by VEGF pathway in human retinal cells

Abstract

Age-related macular degeneration (AMD) that is the main cause of visual impairment and blindness in Europe which is characterized by damages in the central part of the retina, the macula. This degenerative disease of the retina is mainly due to the molecular mechanism involving the production and secretion of vascular endothelial growth factor (VEF). Despite therapeutic advances thanks to the use of anti-VEGF, the progression of the disease is often observed without reverse vision quality. New therapies have emerged such as surgical pharmacological and special attention has been paid to prevention, where diet plays a preponderant role. Indeed, antioxidant such as resveratrol, a polyphenol of grapevines, can prevent VEGF secretion induced by stress from retinal cells. Resveratrol can not only reduce oxidative stress but also alter cellular and molecular signaling as well as physiological effects involved in ocular diseases such as AMD. In this context, we investigate the potential effect of red wine extract (RWE) on the secretion and its signaling pathway in human retinal cells ARPE-19. In order to investigate the effect of RWE in ARPE-19, a quantitative and qualitative analysis of the RWE was performed by HPLC MS/MS. We highlight that RWE are able to decreased whether the protein expression and the secretion of VEGF-A from ARPE-19 in a concentration-dependent manner. This alteration of VEGF-A production is associated with a decreased of VEGF-receptor2 (VEGF-R2) protein expression and its phosphorylated intracytoplasmic domain. Afterwards, kinase pathway activation is disturbing and RWE prevents the phosphorylation of MEK and ERK 1/2 in human retinal cells ARPE-19. According to our results, polyphenolic cocktails could present a potential interest in a prevention strategy against AMD.

Acknowledgments:

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), the “Bureau Interprofessionnel des Vins de Bourgogne” (BIVB), and by the Bordeaux Metabolome Facility and MetaboHUB (ANR-11-INBS-0010) project