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Expression of hypoxia-inducible factor-1α and the protein products of its target genes in diabetic fibrovascular epiretinal membranes
  1. Ahmed M Abu El-Asrar1,
  2. Luc Missotten2,
  3. Karel Geboes3
  1. 1Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
  2. 2Department of Ophthalmology, University of Leuven, Leuven, Belgium
  3. 3Laboratory of Histochemistry and Cytochemistry, University of Leuven, Leuven, Belgium
  1. Correspondence to: Professor A M Abu El-Asrar Department of Ophthalmology, King Abdulaziz University Hospital, Airport Road, PO Box 245, Riyadh 11411, Saudi Arabia;abuasrar{at}


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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  • Published Online First 17 January 2007

  • Competing interests: None declared.