The Sustained Delivery of Resveratrol or a Defined Grape Powder Inhibits New Blood Vessel Formation in a Mouse Model of Choroidal Neovascularization

Abstract

The objective of this study was to determine whether resveratrol or a defined, reconstituted grape powder can attenuate the formation of new blood vessels in a mouse model of choroidal neovascularization (CNV). To accomplish this objective, C57BL/6J mice were randomized into control or treatment groups which received either resveratrol or grape powder by daily oral gavage, resveratrol or grape powder delivered ad libitum through the drinking water, or resveratrol by slow release via implanted osmotic pumps. A laser was used to rupture Bruch’s membrane to induce CNV which was then detected in sclerochoroidal eyecups stained with antibodies against intercellular adhesion molecule-2. CNV area was measured using fluorescence microscopy and Image J software. Ad libitum delivery of both resveratrol and grape powder was shown to significantly reduce the extent of CNV by 68% and 57%, respectively. Parallel experiments conducted in vitro demonstrated that resveratrol activates p53 and inactivates Akt/protein kinase B in choroidal endothelial cells, contributing to its anti-proliferative and anti-migratory properties. In addition resveratrol was shown to inhibit the formation of endothelial cell networks, augmenting its overall anti-angiogenic effects. The non-toxic nature of resveratrol makes it an especially attractive candidate for the prevention and/or treatment of CNV.

Modifying Choroidal Neovascularization Development with a Nutritional Supplement in Mice

“…The effect of oral resveratrol (25–50 mg/kg/day) has been shown to reduce macrophage infiltration and inflammatory and angiogenic (VEGF) cytokines in the RPE-choroid complex in a murine model of laser CNV [ 44 ]. Kanavi et al [ 45 ] found that resveratrol inhibited Akt/protein kinase B activity in choroidal endothelial cells, which is consistent with the anti-migratory properties of resveratrol that have been observed in vitro . Resveratrol also inhibits branching and network formation of choroidal endothelial cells, in vitro correlates of angiogenesis.…”

Resveratrol, in its natural combination in whole grape, for health promotion and disease management

“…Kanavi and colleagues have shown that sustained delivery of resveratrol or a defined grape powder inhibited new blood vessel formation in a mouse model of CNV. 35 The authors argued that the antiangiogenic effects of these compounds are comparable to those obtained with ranibizumab or bevacizumab, which are recombinant monoclonal antibodies used to blocks angiogenesis in human patients. 35 …”

“…Kanavi et al have shown that sustained delivery of resveratrol or a defined grape powder inhibited new blood vessel formation in a mouse model of CNV. 35 The authors argued that the antiangiogenic effects of these compounds are comparable to those obtained with ranibizumab or bevacizumab, which are recombinant monoclonal antibodies used to blocks angiogenesis in human patients. 35 Metabolic syndrome is a disorder of energy use and storage and is clinically diagnosed when three of the five following conditions are present: abdominal obesity, higher blood pressure, elevated fasting plasma glucose, excessive serum triglycerides, and decrease in high-density cholesterol (HDL) levels.…”

SIRT1 mediated inhibition of VEGF/VEGFR2 signaling by Resveratrol and its relevance to choroidal neovascularization

“…Recent reports have shown that RSV can suppress hypoxia-induced VEGF expression and secretion in an immortalized endothelial cell line derived from monkey retina/choroid [7], human adult RPE cells [8] and macrophages [9]. Furthermore, systemic application of RSV inhibits angiogenesis in murine CNV models [9, 10]. In this study, we show for the first time, that the inhibition of VEGF/VEGFR2 signaling in low passage human RPE and endothelial cells is mediated, at least in part, through SIRT1, providing evidence for using RSV or targeting SIRT1 as a potential therapeutic approach for CNV.…”