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Nagineni CN, Raju R, Nagineni KK, et al. Resveratrol Suppresses Expression of VEGF by Human Retinal Pigment Epithelial Cells: Potential Nutraceutical for Age-related Macular Degeneration. Aging Dis. 2014;5(2):88-100doi: 10.14366/AD.2014.050088.
Nagineni, C. N., Raju, R., Nagineni, K. K., Kommineni, V. K., Cherukuri, A., Kutty, R. K., Hooks, J. J., & Detrick, B. (2014). Resveratrol Suppresses Expression of VEGF by Human Retinal Pigment Epithelial Cells: Potential Nutraceutical for Age-related Macular Degeneration. Aging and disease, 5(2), 88-100. https://doi.org/10.14366/AD.2014.050088
Nagineni, Chandrasekharam N, et al. "Resveratrol Suppresses Expression of VEGF by Human Retinal Pigment Epithelial Cells: Potential Nutraceutical for Age-related Macular Degeneration." Aging and disease vol. 5,2 (2014): 88-100. doi: https://doi.org/10.14366/AD.2014.050088
Nagineni CN, Raju R, Nagineni KK, Kommineni VK, Cherukuri A, Kutty RK, Hooks JJ, Detrick B. Resveratrol Suppresses Expression of VEGF by Human Retinal Pigment Epithelial Cells: Potential Nutraceutical for Age-related Macular Degeneration. Aging Dis. 2014 Apr 01;5(2):88-100. doi: 10.14366/AD.2014.050088. eCollection 2014 Apr. PMID: 24729934; PMCID: PMC3966676.
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Aging Dis. 2014 Apr 01;5(2):88-100. doi: 10.14366/AD.2014.050088. eCollection 2014 Apr.

Resveratrol Suppresses Expression of VEGF by Human Retinal Pigment Epithelial Cells: Potential Nutraceutical for Age-related Macular Degeneration.

Aging and disease

Chandrasekharam N Nagineni, Raghavan Raju, Krishnasai K Nagineni, Vijay K Kommineni, Aswini Cherukuri, R Krishnan Kutty, John J Hooks, Barbara Detrick

Affiliations

  1. Laboratory of Immunology, National Eye Institute, NIH, Bethesda, Maryland, USA.
  2. Departments of Medical Laboratory, Imaging and Radiological Sciences, and Biochemistry and Molecular Biology, Georgia Regents University, Augusta, Georgia, USA.
  3. School of Public Policy, University of Maryland, College Park, Maryland, USA.
  4. Laboratory of Retinal Cell and Molecular Biology, National Eye institute, NIH, Bethesda, Maryland.
  5. Department of Pathology, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA.

PMID: 24729934 PMCID: PMC3966676 DOI: 10.14366/AD.2014.050088

Abstract

Age-related macular degeneration (AMD) is a sight threating retinal eye disease that affects millions of aging individuals world-wide. Choroid-retinal pigment epithelium (RPE)-neuroretina axis in the posterior compartment of the eye is the primary site of AMD pathology. There are compelling evidence to indicate association of vascular endothelial growth factors (VEGF) to AMD. Here, we report the inhibitory actions of resveratrol (RSV) on inflammatory cytokine, TGF-β and hypoxia induced VEGF secretion by human retinal pigment epithelial cells (HRPE). HRPE cultures prepared from aged human donor eyes were used for the studies in this report. HRPE secreted both VEGF-A and VEGF-C in small quantities constitutively. Stimulation with a mixture of inflammatory cytokines (IFN-γ, TNF-α, IL-1β), significantly increased the secretion of both VEGF-A and VEGF-C. RSV, in a dose dependent (10-50 uM) manner, suppressed VEGF-A and VEGF-C secretion induced by inflammatory cytokines significantly. RT-PCR analysis indicated that effects of RSV on VEGF secretion were possibly due to decreased mRNA levels. TGF-β and cobalt chloride (hypoxia mimic) also upregulated HRPE cell production of VEGF-A, and this was inhibited by RSV. In contrast, RSV had no effect on anti-angiogenic molecules, endostatin and pigment epithelial derived factor secretion. Studies using an in vitro scratch assay revealed that wound closure was also inhibited by RSV. These results demonstrate that RSV can suppress VEGF secretion induced by inflammatory cytokines, TGF-β and hypoxia. Under pathological conditions, over expression of VEGF is known to worsen AMD. Therefore, RSV may be useful as nutraceutical in controlling pathological choroidal neovascularization processes in AMD.

Keywords: Age-related macular degeneration; Cytokines; Resveratrol; Retina; Retinal pigment epithelium; SIRT1; VEGF

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