Resveratrol suppresses expression of VEGF by human retinal pigment epithelial cells: Potential nutraceutical for age-related macular degeneration

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

Research output: Contribution to journalArticle

42 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)88-100
Number of pages13
JournalAging and Disease
Volume5
Issue number2
DOIs
StatePublished - Jan 1 2014

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Retinal Pigments
Macular Degeneration
Dietary Supplements
Vascular Endothelial Growth Factors
Epithelial Cells
Vascular Endothelial Growth Factor C
Vascular Endothelial Growth Factor A
Cytokines
Pathologic Neovascularization
Endostatins
Retinal Diseases
Choroidal Neovascularization
Choroid
Eye Diseases
resveratrol
human VEGFA protein
Retinal Pigment Epithelium
Interleukin-1
Cell Culture Techniques
Pathology

Keywords

  • Age-related macular degeneration
  • Cytokines
  • Resveratrol
  • Retina
  • Retinal pigment epithelium
  • SIRT1
  • VEGF

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Geriatrics and Gerontology
  • Clinical Neurology
  • Cell Biology

Cite this

Resveratrol suppresses expression of VEGF by human retinal pigment epithelial cells : Potential nutraceutical for age-related macular degeneration. / Nagineni, Chandrasekharam N.; Raju, Raghavan Pillai; Nagineni, Krishnasai K.; Kommineni, Vijay K.; Cherukuri, Aswini; Kutty, R. Krishnan; Hooks, John J.; Detrick, Barbara.

In: Aging and Disease, Vol. 5, No. 2, 01.01.2014, p. 88-100.

Research output: Contribution to journalArticle

Nagineni, Chandrasekharam N. ; Raju, Raghavan Pillai ; Nagineni, Krishnasai K. ; Kommineni, Vijay K. ; Cherukuri, Aswini ; Kutty, R. Krishnan ; Hooks, John J. ; Detrick, Barbara. / Resveratrol suppresses expression of VEGF by human retinal pigment epithelial cells : Potential nutraceutical for age-related macular degeneration. In: Aging and Disease. 2014 ; Vol. 5, No. 2. pp. 88-100.
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AU - Kommineni, Vijay K.

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