Study Title:

Resveratrol May Help Wet Age Related Macular Degeneration

Study Abstract

PURPOSE:
Resveratrol, a polyphenolic phytoalexin present in red wine, has a protective role against tumor-induced angiogenesis. Exudative age-related macular degeneration is characterized by hypoxia-induced choroidal vascular endothelial cell (CVEC) proliferation. In this study, we evaluated the effect of resveratrol on hypoxic CVECs and the underlying signaling pathways involved.

METHODS:
CVECs (RF/6A) after induction of hypoxia with cobalt chloride (CoCl2, 200 μM) were exposed to increasing doses of resveratrol (2, 4, 6, 8, 10, and 12 μg/ml). Cell viability was measured with 4-[3-(4Iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1, 3-benzene disulfonate (WST-1) colorimetric assay. The effect of resveratrol on hypoxia-induced vascular endothelial growth factor (VEGF) release was analyzed with enzyme-linked immunosorbent assay. The mechanistic pathway was further evaluated by analyzing phosphorylated stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) using immunoblot and cleaved caspase-3 with In-Cell enzyme-linked immunosorbent assay.

RESULTS:
Resveratrol inhibited hypoxic CVEC proliferation. Hypoxia-induced VEGF release (30.9±2.6 pg/ml) was inhibited in a dose-dependent fashion by 2, 4, 6, 8, 10, and 12 μg/ml resveratrol to 12.4±2.1, 11.0±1.9, 10.3±3.0, 7.5±1.9, 5.5±2.0, and 5.5±2.3 pg/ml, respectively. SAPK/JNK increased by 1.8-fold and 3.9-fold after treatment with 4 and 12 μg/ml resveratrol, respectively. Significant increase in caspase-3 levels was observed with 12 μg/ml resveratrol.

CONCLUSIONS:
Our study demonstrates that resveratrol suppresses hypoxic CVEC proliferation through activation of the SAPK/JNK pathway. Resveratrol, a nutritional supplement and inhibitor of CVECs, may be a useful adjunct to current anti-VEGF therapy in wet age-related macular degeneration.

Study Information

Balaiya S, Murthy RK, Chalam KV.
Resveratrol inhibits proliferation of hypoxic choroidal vascular endothelial cells.
Mol Vis.
2013 November
Department of Ophthalmology, University of Florida College of Medicine, Jacksonville, FL.

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