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Vascular endothelial growth factor C promotes survival of retinal vascular endothelial cells via vascular endothelial growth factor receptor-2
  1. Bojun Zhao1,
  2. Gill Smith1,
  3. Jun Cai1,
  4. Aihua Ma1,
  5. Mike Boulton2
  1. 1Cell and Molecular Biology Unit, School of Optometry and Vision Sciences, Cardiff University, Cardiff, UK
  2. 2Department of Ophthalmology and Vision Sciences, University of Texas Medical Branch, Galveston, Texas, USA
  1. Correspondence to: Professor M Boulton Department of Ophthalmology and Visual Sciences, The University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555-1106, USA; boultonm{at}utmb.edu

Abstract

Aim: To determine vascular endothelial growth factor C (VEGF-C) expression in retinal endothelial cells, its antiapoptotic potential and its putative role in diabetic retinopathy.

Method: Cultured retinal endothelial cells and pericytes were exposed to tumour necrosis factor (TNF)α and VEGF-C expression determined by reverse transcriptase-polymerase chain reaction. Secreted VEGF-C protein levels in conditioned media from endothelial cells were examined by western blotting analysis. The ability of VEGF-C to prevent apoptosis induced by TNFα or hyperglycaemia in endothelial cells was assessed by flow cytometry. The expression of VEGF-C in diabetic retinopathy was studied by immunohistochemistry of retinal tissue.

Result: VEGF-C was expressed by both vascular endothelial cells and pericytes. TNFα up regulated both VEGF-C and vascular endothelial growth factor receptor-2 (VEGFR)-2 expression in endothelial cells in a dose-dependent manner, but had no effect on VEGFR-3. Flow cytometry results showed that VEGF-C prevented endothelial cell apoptosis induced by TNFα and hyperglycaemia and that the antiapoptotic effect was mainly via VEGFR-2. In pericytes, the expression of VEGF-C mRNA remained stable on exogenous TNFα treatment. VEGF-C immunostaining was increased in retinal vessels in specimens with diabetes compared with retinal specimens from controls without diabetes.

Conclusion: In retinal endothelial cells, TNFα stimulates the expression of VEGF-C, which in turn protects endothelial cells from apoptosis induced by TNFα or hyperglycaemia via VEGFR-2 and thus helps sustain retinal neovascularisation.

  • GAPDH, glyceraldehyde-3-phosphate dehydrogenase
  • MEC, microvascular retinal endothelial cell
  • PCR, polymerase chain reaction
  • PDR, proliferative diabetic retinopathy
  • RT-PCR, reverse transcriptase-polymerase chain reaction
  • siRNA, small interfering RNA
  • TNF, tumour necrosis factor
  • VEGF, vascular endothelial growth factor
  • VEGFR, vascular endothelial growth factor receptor

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Footnotes

  • Published Online First 30 August 2006

  • Funding: This work was supported by the Wellcome Trust.

  • Competing interests: None.

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