Expression of stem cell factor/c-kit signaling pathway components in diabetic fibrovascular epiretinal membranes.
OBJECTIVE
Stem cell factor (SCF)/c-kit signaling promotes recruitment of endothelial progenitor cells and contributes to ischemia-induced new vessel formation. We investigated the expression of the components of this pathway, including c-kit, SCF, granulocyte colony-stimulating factor (G-CSF), endothelial nitric oxide synthase (eNOS), and the chemokine receptor CXCR4, in proliferative diabetic retinopathy (PDR) epiretinal membranes.


METHODS
Membranes from eight patients with active PDR and 12 patients with inactive PDR were studied by immunohistochemistry.


RESULTS
Blood vessels expressed c-kit, SCF, G-CSF, eNOS, and CXCR4 in 18, 15, 19, 20, and 20 out of 20 membranes, respectively. Significant correlations were detected between the number of blood vessels expressing CD34 and the number of blood vessels expressing SCF (r=0.463; p=0.04), G-CSF (r=0.87; p<0.001), eNOS (r=0.864; p<0.001), and CXCR4 (r=0.864; p<0.001). Stromal cells expressed c-kit, SCF, eNOS, and CXCR4 in 19, 15, 20, and 20 membranes, respectively. The numbers of blood vessels expressing CD34 (p=0.005), c-kit (p=0.03), G-CSF (p=0.007), eNOS (p=0.001), and CXCR4 (p=0.018) and stromal cells expressing c-kit (p=0.013), SCF (p<0.001), eNOS (p=0.048), and CXCR4 (p=0.003) were significantly higher in active membranes than in inactive membranes.


CONCLUSIONS
SCF/c-kit signaling might contribute to neovascularization 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
Opdenakker
Ghislain
G
Van Damme
Jo
J
Geboes
Karel
K
D000328:Adult; D003930:Diabetic Retinopathy / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D019773:Epiretinal Membrane / Q000378:metabolism*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism; D012171:Retinal Vessels / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D019089:Stem Cell Factor / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism
C527276:CXCR4 protein, human; D019718:Receptors, CXCR4; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D019009:Proto-Oncogene Proteins c-kit