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. 2010 Jun 15:16:1098-107.

Expression of stem cell factor/c-kit signaling pathway components in diabetic fibrovascular epiretinal membranes

Ahmed M Abu El-Asrar  1 , Sofie Struyf, Ghislain Opdenakker, Jo Van Damme, Karel Geboes
Affiliations

Expression of stem cell factor/c-kit signaling pathway components in diabetic fibrovascular epiretinal membranes

Ahmed M Abu El-Asrar et al. Mol Vis. .

Abstract

Purpose: 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.

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Figures

Figure 1
Figure 1
Negative control slide that was treated identically with an irrelevant antibody. No labeling was observed (A: original magnification 40×). Immunohistochemical staining for CD34. Blood vessels and stromal cells showed immunoreactivity for CD34 (B: original magnification 40×). Immunohistochemical staining for c-kit. Vascular endothelial cells (C: original magnification 100×) and stromal cells (D: original magnification 40×) showed immunoreactivity for c-kit.
Figure 2
Figure 2
Immunohistochemical staining for stem cell factor (SCF). Vascular endothelial cells and stromal cells expressed strong immunoreactivity for SCF in a membrane from a patient with active proliferative diabetic retinopathy (PDR). A: Low power, original magnification 40×. B: high-power, original magnification 100×. SCF immunoreactivity is absent in a membrane from a patient with inactive PDR. Note that the membrane is composed mostly of fibrous tissue (C: original magnification 40×). Immunohistochemical staining for granulocyte colony-stimulating factor (G-CSF). G-CSF immunoreactivity was observed in vascular endothelial cells (D: original magnification 100×). Immunohistochemical staining for endothelial nitric oxide synthase (eNOS). Immunoreactivity for eNOS was observed in vascular endothelial cells (E: original magnification 100×) and stromal cells (F: Low-power, original magnification 40× and G: high-power, original magnification 100×).
Figure 3
Figure 3
Immunohistochemical staining for CXCR4. Immunoreactivity for CXCR4 was observed in vascular endothelial cells (A: original magnification 100×) and stromal cells (B: original magnification 40×). Double immunohistochemistry for CXCR4 (red) and c-kit (blue). Cells co-expressing CXCR4 and c-kit were observed in the vascular endothelium (arrows) and in close association with blood vessels (arrowheads). C: original magnification 100×.
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