title: Expression of hypoxia-inducible factor-1alpha and the protein products of its target genes in diabetic fibrovascular epiretinal membranes.
abstract: OBJECTIVE
  To investigate the expression of the hypoxia-inducible factor-1alpha (HIF-1alpha) 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-1alpha, 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-1alpha (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-1alpha, 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.
authors.affiliation: Department of Ophthalmology, King Abdulaziz University Hospital, Airport Road, PO Box 245, Riyadh 11411, Saudi Arabia. abuasrar@ksu.edu.sa
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Abu El-Asrar
authors.forename: Luc
authors.initials: L
authors.lastname: Missotten
authors.forename: Karel
authors.initials: K
authors.lastname: Geboes
mesh_terms: D042702:Angiopoietin-2 / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D002455:Cell Division; D003930:Diabetic Retinopathy / Q000378:metabolism* / Q000473:pathology; D019773:Epiretinal Membrane / Q000378:metabolism* / Q000473:pathology; D004921:Erythropoietin / Q000378:metabolism; D005136:Eye Proteins / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism; D015843:Serpins / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D042702:Angiopoietin-2; D018952:Antigens, CD34; D004921:Erythropoietin; D005136:Eye Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019394:Ki-67 Antigen; D009414:Nerve Growth Factors; D015843:Serpins; D042461:Vascular Endothelial Growth Factor A; D000099174:Pigment Epithelium-Derived Factor; C467484:VEGFA protein, human