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

Abstract

Abstract Purpose 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 8 patients with active PDR and 9 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, 7 and 7 out of 17 membranes, respectively. There were significant correlations between number of blood vessels expressing CD34 and number of blood vessels expressing CD133 (rs=0.646; p=0.005), VEGFR‐2 (rs=0.704; p=0.002), CD14 (rs=0.564; p=0.018), and SDF‐1 (rs=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. 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.