Involvement of Circulating Endothelial Progenital Cells and Vasculogenic Factors in Diabetic Retinopathy

ABSTRACT

PURPOSE: Retinal neovascularization in diabetes has been thought to follow the release of local angiogenic factors in the retina. We hypothesized that neovascularization of diabetic retinopathy is a systemic vasculogenesis rather than a local angiogenesis. Thus, we evaluated the concentrations of circulating endothelial progenitor cells (EPCs) and stem cell modulation factors such as vascular endothelial growth factor (VEGF), erythropoietin (EPO), and substance p (SP) in the peripheral blood of diabetic retinopathy patients. METHODS: We studied 15 normal controls and 45 Type 2 diabetic patients [non-DR group (n=15), NPDR group (n=15), and PDR group (n=15)]. We measured circulating CD34+mononuclear cells (CD34+MNCs) and c-Kit+mononuclear cells (c-Kit+MNCs) by flow cytometry. VEGF, EPO and SP in the peripheral blood were measured by ELISA. RESULTS: The circulating CD34+MNCs and c-Kit+MNCs increased in the NPDR and PDR groups compared with the control group (P<0.01). The serum level of VEGF was increased in the NPDR and PDR groups compared with the control group (P<0.05). The level of EPO was exclusively elevated in the non-DR group compared with the other three groups (P<0.01). The circulating SP level increased in the NPDR and PDR groups compared with the control group (P<0.05). CONCLUSIONS: The present study is the first to demonstrate that CD34+MNCs, c-Kit+MNCs and their modulator are elevated in diabetic retinopathy patients. Therefore, it is possible that circulating EPCs and serum VEGF, EPO and SP may be involved in the progression of diabetic retinopathy.