Increased Clonogenic Potential of Endothelial Progenitor Cells (EPCs) in Type 1 Diabetic Patients with Early Non Proliferative Diabetic Retinopathy

Abstract

Purpose: : To gain insight into the behavior of endothelial progenitor cells (EPCs) at different stages of diabetic retinopathy in type 1 diabetic patients. The initial lesions caused by diabetes in retinal vessels include vascular cell death and vessel remodeling. A subgroup of patients may go on to develop proliferative diabetic retinopathy (PDR), characterized by the formation of incompetent capillaries that cause vitreous hemorrhage and/or retinal detachment and severe visual impairment. The recent identification of circulating EPCs has generated questions about whether and how these cells interface with vascular pathologies.

Methods: : In type 1 diabetic patients with (A) < 20 years of diabetes with signs of non-proliferative retinopathy (n=15), (B) > 25 years of diabetes without retinopathy (n=20) and (iii) age-and gender-matched nondiabetic controls (n=20), we measured the number of circulating EPCs (CD45^dim, CD34⁺,VEGFR-2⁺; see NEJM 2008; 359:763) by flow cytometry; their clonogenic potential by the Hill’s assay; and plasma concentrations by ELISA of VEGF and SDF-1, the two cytokines known to mobilize EPC. All measurements were performed when plasma glucose levels were between 70 and 200 mg/dl.

Results: : The clonogenic potential of EPCs was significantly increased in group A when compared to group B (p<0.003) and to non diabetic controls (p<0.01). In contrast, the number of circulating EPCs and the cytokines plasma levels were similar in the three groups. The differences in clonogenic potential between the diabetic groups were not explained by different glycemic control (blood glucose and HbA1c). Within group A, no differences in clonogenic potential were noted between patients with initial (ETDRS 20) as compared to mild (ETDRS 35) degree of retinopathy.

Conclusions: : In a portion of patients with type 1 diabetes, the onset of lesions in retinal vessels is accompanied by increased clonogenic potential of EPCs. It will be important to learn whether the increased clonogenic potential relates in a protective or in an accelerating way to the course of retinopathy in the individual patients. Longitudinal studies are now under way.

Keywords: diabetic retinopathy • cytokines/chemokines • flow cytometry