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K. Tan, A. Cutler, P. Nerone, B. Anand-Apte; Dysfunction of Circulating Endothelial Progenitor Cells in Patients With Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4385.
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We proposed to determine whether there are quantitative and/or functional differences in the various EPC populations in patients who develop PDR.
To quantify circulating colony-forming unit endothelial cells (CFU-ECs) and endothelial colony-forming cell (ECFC) EPC populations, we isolated mononuclear cells (MNCs) by density centrifugation from peripheral blood obtained from healthy non-diabetic controls, diabetic patients without DR, diabetic patients with non-proliferative DR (NPDR), and patients with PDR. MNCs were analyzed by fluorescence-activated cell sorting (FACS) analysis for positivity to CD34, CD45, CD133, and vascular endothelial growth factor receptor-2 (VEGFR-2). ECFC colonies were generated from MNCs, expanded and analyzed for expression of various angiogenic proteins and cytokines in the presence and absence of glucose. Angiogenic mobility potential was analyzed using VEGF as the target factor.
Compared to healthy controls and diabetic patients without DR, patients who have NPDR have higher levels of circulating CD133+ cells [14.4% ± 3.2% (NPDR) vs 2.8% ± 1.5% (healthy) vs 1.8% ± 2.1% (diabetes without DR), p = 0.007]. In addition, higher levels of circulating CD34+ CD45- ECFC progenitors were observed in patients with PDR compared to healthy controls [0.051% ± 0.005% (healthy) vs 0.096% ± 0.024% (PDR), p = 0.036]. ECFCs from normal controls exposed to a high concentration of glucose showed decreased matrix metalloproteinase-2 (MMP-2) expression and reduced vasculogenic mobility in vitro.
EPCs (CFU-ECs and ECFCs) are increased in early diabetic retinopathy, and levels of ECFCs are higher in patients with PDR. However, when exposed to a hyperglycemic environment, ECFCs may lose their ability to function as effective pro-angiogenic precursors.
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