Involvement of circulating endothelial progenitor cells and vasculogenic factors in the pathogenesis of diabetic retinopathy.
OBJECTIVE
Retinal neovascularization in diabetes has been thought to follow the release of local angiogenic factors in the retina. We hypothesize that neovascularization of diabetic retinopathy is a systemic vasculogenesis rather than a local angiogenesis. Thus, we evaluate 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 II diabetic patients (no DR group (n=15), NPDR group (n=15), and PDR group (n=15)). We measured circulating CD34+mononuclear cells (CD34+MNCs), 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). Serum level of VEGF increased in the NPDR and PDR groups compared with the control group (P<0.05). The level of Epo elevated exclusively in the no DR group compared with the other three groups (P<0.01). Circulating SP level increased in the NPDR and PDR groups compared with the control group (P<0.05). SP and CD34+MNCs were shown to have increased correlation according to the diabetic retinopathy in the NPDR and PDR groups (r=0.440, P<0.05 and r=0.460, P<0.05, respectively).


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 Epo, VEGF, and SP may be involved in the progression of diabetic retinopathy.
Lee
I G
IG
Department of Ophthalmology, College of Medicine, Chung Ang University, Seoul, Korea.
Chae
S L
SL
Kim
J C
JC
D000368:Aged; D000369:Aged, 80 and over; D043925:Angiogenesis Inducing Agents / Q000097:blood*; D018952:Antigens, CD34 / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000473:pathology*; D003930:Diabetic Retinopathy / Q000097:blood / Q000473:pathology*; D004730:Endothelium, Vascular / Q000473:pathology; D004921:Erythropoietin / Q000097:blood; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015861:Retinal Neovascularization / Q000097:blood / Q000473:pathology; D012720:Severity of Illness Index; D013234:Stem Cells / Q000473:pathology*; D013373:Substance P / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D043925:Angiogenesis Inducing Agents; D018952:Antigens, CD34; D042461:Vascular Endothelial Growth Factor A; D004921:Erythropoietin; D013373:Substance P