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Originally published In Press as doi:10.1167/iovs.08-1748 on August 21, 2008
 (Investigative Ophthalmology and Visual Science. 2009;50:392-398.)
© 2009 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.08-1748
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Correlation of Different Circulating Endothelial Progenitor Cells to Stages of Diabetic Retinopathy: First In Vivo Data

Simon Brunner,1,2,3 Gerit-Holger Schernthaner,3,4 Miriam Satler,4 Marie Elhenicky,4 Florian Hoellerl,4 Katharina E. Schmid-Kubista,1,2 Florian Zeiler,1,2 Susanne Binder,1,2 and Guntram Schernthaner5

1From the Departments of Ophthalmology and 5Internal Medicine I, Rudolf Foundation Clinic Vienna, Vienna, Austria; 2The Ludwig Boltztmann Institute for Retinology and Biomicroscopic Laser Surgery, Vienna, Austria; and the 4Department of Internal Medicine II, Division of Angiology, Medical University, Vienna, Austria.

PURPOSE. To investigate vasculogenic circulating progenitor cells (CPCs), endothelial progenitor cells (EPCs), and mature EPCs in patients with type 1 diabetes mellitus (T1DM) with or without diabetic retinopathy (DR).

METHODS. A case-control study comparing 90 patients with T1DM with and without DR was performed. Patients were studied and staged for retinopathy according to the Early Treatment of Diabetic Retinopathy Study (ETDRS) classification. Ninety patients were included: 30 without DR (control [CO]), 30 with mild nonproliferative DR (mNPDR), 10 with moderate-severe NPDR (msNPDR), 10 with mild-moderate proliferative diabetic retinopathy (mmPDR), and 10 with high-risk PDR (hrPDR). CPCs (CD34/CD133), EPCs (CD34/CD133/CD309), and mature EPCs (CD34/CD133/CD309/CD31) were enumerated by flow cytometry.

RESULTS. EPCs were reduced in mNPDR (114 ± 66; P < 0.001) and msNPDR (77 ± 40; P = 0.042) compared with CO (244 ± 115). In contrast, EPCs were unchanged in mmPDR (248 ± 155) compared with CO. Strikingly, EPCs were augmented in hrPDR (389 ± 124) compared with all other stages. Numbers of undifferentiated progenitor cells (CPCs) did not differ among CO, mmPDR, and hrPDR. Augmentation (3x) of mature EPCs in hrPDR (325 ± 118; P < 0.001) compared with CO (100 ± 49) but against all other stages of DR was observed. The percentage of mature EPCs/EPCs was augmented in an ETDRS classification-dependent manner.

CONCLUSIONS. In patients with T1DM with DR, EPCs undergo stage-related regulation. In nonproliferative retinopathy, a reduction of EPCs was observed, and in proliferative retinopathy, a dramatic increase of mature EPCs was observed.






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