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Expression of hypoxia-inducible factor-1α and the protein products of its target genes in diabetic fibrovascular epiretinal membranes

Abstract

Aims: To investigate the expression of the hypoxia-inducible factor-1α (HIF-1α) and the protein products of its target genes vascular endothelial growth factor (VEGF), erythropoietin (Epo) and angiopoietins (Angs), and the antiangiogenic pigment epithelium-derived factor (PEDF) in proliferative diabetic retinopathy (PDR) epiretinal membranes.

Methods: Sixteen membranes were studied by immunohistochemical techniques.

Results: Vascular endothelial cells expressed HIF-1α, Ang-2 and VEGF in 15 (93.75%), 6 (37.5%) and 9 (56.25%) membranes, respectively. There was no immunoreactivity for Epo, Ang-1 and PEDF. There were significant correlations between the number of blood vessels expressing the panendothelial marker CD34 and the numbers of blood vessels expressing HIF-1α (r = 0.554; p = 0.026), Ang-2 (r = 0.830; p<0.001) and VEGF (r = 0.743; p = 0.001). The numbers of blood vessels expressing Ang-2 and VEGF in active membranes were higher than that in inactive membranes (p = 0.015 and 0.028, respectively).

Conclusions: HIF-1α, Ang-2 and VEGF may play an important role in the pathogenesis of PDR. The findings suggest an adverse angiogenic milieu in PDR epiretinal membranes favouring aberrant neovascularisation and endothelial abnormalities.

  • Ang, angiopoietin
  • Epo, erythropoietin
  • HIF-1α, hypoxia-inducible factor-1α
  • ICAM-1, intercellular adhesion molecule-1
  • PEDF, pigment epithelium-derived factor
  • PDR, proliferative diabetic retinopathy
  • VEGF, vascular endothelial growth factor

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