Circulating bone-marrow-derived endothelial precursor cells contribute to neovascularization in diabetic epiretinal membranes.
OBJECTIVE
The role of vasculogenesis, recruitment and differentiation of circulating bone-marrow-derived endothelial precursor cells into mature endothelium in proliferative diabetic retinopathy (PDR) remains undefined. We investigated the presence of bone-marrow-derived endothelial precursor cells and the expression of the chemotactic pathway SDF-1 ⁄CXCL12)CXCR4 in PDR epiretinal membranes.


METHODS
Membranes from eight patients with active PDR and nine patients with inactive PDR were studied by immunohistochemistry using antibodies against CD133, vascular endothelial growth factor receptor-2 (VEGFR-2), CD14, SDF-1 and CXCR4.


RESULTS
Blood vessels expressed CD133, VEGFR-2, CD14, SDF-1 and CXCR4 in 10, 10, 10, seven and seven out of 17 membranes, respectively. There were significant correlations between number of blood vessels expressing CD34 and number of blood vessels expressing CD133 (r(s) = 0.646; p = 0.005), VEGFR-2 (r(s) = 0.704; p = 0.002), CD14 (r(s) = 0.564; p = 0.018) and SDF-1 (r(s) = 0.577; p = 0.015). Stromal cells in close association with blood vessels expressed CD133, VEGFR-2, CD14 and CXCR4 in 10, 12, 13 and 14 membranes, respectively. The number of blood vessels expressing CD133 (p = 0.013), VEGFR-2 (p = 0.005), CD14 (p = 0.008) and SDF-1 (p = 0.005), and stromal cells expressing CD133 (p = 0.003), VEGFR-2 (p = 0.013) and CD14 (p = 0.002) was significantly higher in active membranes than in inactive membranes.


CONCLUSIONS
Bone-marrow-derived CD133(+) endothelial progenitor cells and CD14(+) monocytes may contribute to vasculogenesis in PDR.
Abu El-Asrar
Ahmed M
AM
Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia. abuasrar@ksu.edu.sa
Struyf
Sofie
S
Verbeke
Hannelien
H
Van Damme
Jo
J
Geboes
Karel
K
D000071916:AC133 Antigen; D015703:Antigens, CD / Q000378:metabolism; D001854:Bone Marrow Cells / Q000502:physiology*; D054377:Chemokine CXCL12 / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000378:metabolism / Q000503:physiopathology*; D042783:Endothelial Cells / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D019773:Epiretinal Membrane / Q000378:metabolism / Q000503:physiopathology*; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D015861:Retinal Neovascularization / Q000378:metabolism / Q000503:physiopathology*; D012171:Retinal Vessels / Q000378:metabolism / Q000503:physiopathology*; D013234:Stem Cells / Q000502:physiology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D000071916:AC133 Antigen; D015703:Antigens, CD; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D006023:Glycoproteins; D018950:Lipopolysaccharide Receptors; C000606023:PROM1 protein, human; D010455:Peptides; D019718:Receptors, CXCR4; D040301:Vascular Endothelial Growth Factor Receptor-2