Circulating bone-marrow-derived endothelial precursor cells contribute to neovascularization in diabetic epiretinal membranes

Purpose: 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. Conclusion: Bone-marrow-derived CD133+ endothelial progenitor cells and CD14+ monocytes may contribute to vasculogenesis in PDR.