Correlation of different circulating endothelial progenitor cells to stages of diabetic retinopathy: first in vivo data.
OBJECTIVE
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.
Brunner
Simon
S
Department of Ophthalmology, Rudolf Foundation Clinic Vienna, Vienna, Austria. simon.brunner@wienkav.at
Schernthaner
Gerit-Holger
GH
Satler
Miriam
M
Elhenicky
Marie
M
Hoellerl
Florian
F
Schmid-Kubista
Katharina E
KE
Zeiler
Florian
F
Binder
Susanne
S
Schernthaner
Guntram
G
D000328:Adult; D015703:Antigens, CD / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D003930:Diabetic Retinopathy / Q000097:blood*; D004730:Endothelium, Vascular / Q000473:pathology*; D005434:Flow Cytometry; D006442:Glycated Hemoglobin / Q000032:analysis; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans
D015703:Antigens, CD; D015415:Biomarkers; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human