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

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 8 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 number of blood vessels expressing CD34 and 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. Conclusion SCF/c‐kit signaling might contribute to neovascularization in PDR.

Cultivation and characterization of pterygium as an ex vivo study model for disease and therapy

“…The SDF-1/CXCR4 signalling pathway has been described in developmental processes and adult angiogenesis to have a role in vascular endothelial cell migration and proliferation [24]. LESCs themselves possess migratory capacity or positivity for CXCR4 [17], while this marker is expressed by vascular endothelial cells in proliferative diabetic retinopathy membranes as well [25]. The pterygium graft-containing cultures showed 2.5 times less positivity for CXCR4 compared to multi-layered outgrowing cell cultures.…”

Role of matrix metalloproteinase-2 and -9 in the development of diabetic retinopathy

“…The early (i.e., nonproliferative diabetic retinopathy) histological characteristic features of diabetic retinopathy include thickening of basement membrane and the loss of pericytes and endothelial cells, which results in vascular leakage [2][3][4]. At advanced stages (i.e., proliferative diabetic retinopathy), inflammation, ischemia-induced angiogenesis, and expansion of extracellular matrix (ECM) in association with the outgrowth of fibrovascular membranes at the vitreoretinal interface, results in neovascularization and retinal detachment, leading to blindness [5,6]. No recent national populationbased estimate of the prevalence and severity of diabetic retinopathy exists.…”

Ex vivo adherent cultures for ocular disease modeling, characterisation and inflammation studies

“…LESCs themselves possess migratory capacity or positivity for CXCR4 (23), while this marker is expressed by vascular endothelial cells in proliferative diabetic retinopathy membranes as well (28). The pterygium graft-containing cultures showed 2.5 times less positivity for CXCR4 compared to the multi-layered outgrowing cell cultures.…”