Expression of hypoxia-inducible factor-1alpha and the protein products of its target genes in diabetic fibrovascular epiretinal membranes.
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.
Abu El-Asrar
Ahmed M
AM
Department of Ophthalmology, King Abdulaziz University Hospital, Airport Road, PO Box 245, Riyadh 11411, Saudi Arabia. abuasrar@ksu.edu.sa
Missotten
Luc
L
Geboes
Karel
K
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
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