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Vascular endothelial growth factor C promotes survival of retinal vascular endothelial cells via vascular endothelial growth factor receptor-2


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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