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Chandra N. Nagineni, Barbara Detrick, John J. Hooks; Resveratrol Suppresses Cytokine and Hypoxia Induced Expression of VEGF by Human RPE cells: Potential Use as a Neutraceutical for Age-related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2296.
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Vascular endothelial growth factors (VEGF) play a critical role in choroidal neovascularization (CNV) in age related macular degeneration (AMD). Retinal pigment epithelium (RPE) is a key tissue involved in AMD pathogenesis. Our previous studies have shown that inflammatory cytokine mix (ICM) and TGF-β induce VEGF expression by human RPE cells (HRPE). In this study, we evaluated the role of resveratrol (RSV) in regulating the expression of VEGF by HRPE.
Primary cultures of HRPE derived from adult donor eyes were used. Confluent cultures grown in 24 well plates were treated with ICM (IFN-γ, 20 u/ml+TNF-α, 2 ng/ml+IL-1β, 2 ng/ml), TGF-β1 (2 ng/ml) or cobalt chloride (Cocl2, hypoxia mimic) in the presence of RSV in serum free medium for 24 h. Levels of secreted VEGF-A, VEGF-C, other cytokines and chemokines were determined by ELISA. VEGF mRNA expression was evaluated by RT-PCR.
VEGF-A secretion was significantly enhanced by HRPE cells by ICM, TGF-β1 and Cocl2. RSV at 10 - 50 uM concentration exhibited dose dependent inhibition of VEGF-A secretion upregulated by ICM, TGF-β and Cocl2. RSV at 50 uM slightly decreased constitutively secreted VEGF-A. VEGF-C secretion was significantly enhanced in HRPE cells by ICM but not by TGF-β and Cocl2. RSV at 10 - 50 uM suppressed VEGF-C secretion induced by ICM in HRPE cells by 40 to 80%. These data demonstrate that RSV is a potent suppresser of VEGF secretion elevated during hypoxic and inflammatory conditions.
RSV suppressed the HRPE secretion of VEGF-A and VEGF-C that was upregulated by ICM in HRPE. VEGF-A secretion enhanced by TGF-β and hypoxia was also suppressed by RSV. Our results suggest that RSV inhibits expression of VEGF by HRPE cells under a variety of conditions such as inflammation and hypoxia. The potential usefulness of RSV, present in grapes and other plant derived products, may be considered as a neutraceutical in AMD.
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