title: Dysfunction of circulating endothelial progenitor cells in type 1 diabetic rats with diabetic retinopathy.
abstract: OBJECTIVE
  To investigate the role of endothelial progenitor cell (EPC) in the pathogenesis of diabetic retinopathy (DR) in streptozotocin (STZ)-induced type 1 diabetes mellitus (T1DM) rats.
  
  
  METHODS
  A total of 160 male Wistar rats (12 weeks old; 250-350 g) were randomly assigned into four groups (n = 40 for each), including control (group 1, no treatment), T1DM1 (group 2, 1 month after 50 mg/kg of STZ, single i.p.), T1DM3 (group 3, 3 months after 50 mg/kg of STZ, single i.p.), T1DM6 (group 4, 6 months after 50 mg/kg of STZ, single i.p.). Enumeration of circulating EPC from peripheral blood was measured by flow cytometry. EPC from bone marrow of rats was cultured in vitro to evaluate its function of proliferation, adhesion, and migration activities. Plasma levels of vascular endothelial growth factor (VEGF) and nitric oxide (NO) were measured by enzyme-linked immunosorbent assay (ELISA). Retinal sections were imaged by light microscopy and a transmission electron microscope (TEM).
  
  
  RESULTS
  The numbers of circulating EPC were significantly decreased in diabetic groups compared with the control group. Impaired proliferation, adhesion, and migratory activities of cultured EPC were observed in diabetic groups. There were significantly higher levels of plasma VEGF but lower levels of plasma NO in diabetic groups than those in non-diabetic controls. The significantly reduced thickness and obvious disorganized retinal cell layers were seen in T1DM DR rats. In the diabetic groups, we also found that T1DM rats developed telangiectatic vessels, vacuolar degeneration of ganglion cells, and thickened capillary basement membrane with capillary lumen stenosis in the retina. Significantly raised EPC numbers during DR formation and progression were also found.
  
  
  CONCLUSIONS
  The reduced numbers and impaired function of circulating EPC may contribute to the pathogenesis of DR in T1DM rats.
authors: Department of Ophthalmology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Tianjin 300052, China.
authors: Wei
authors: W
authors: Zhang
authors: Hua
authors: H
authors: Yan
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D003930:Diabetic Retinopathy / Q000503:physiopathology*; D042783:Endothelial Cells / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D001786:Blood Glucose; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III
references: Proc Natl Acad Sci U S A. 2008 May 6;105(18):6620-5
references: 18443294
references: Diabetes Care. 2004 Oct;27(10):2540-53
references: 15451934
references: Science. 1997 Feb 14;275(5302):964-7
references: 9020076
references: Diabetes. 2006 Jan;55(1):102-9
references: 16380482
references: J Med Food. 2012 Apr;15(4):391-8
references: 22191573
references: Int J Artif Organs. 2011 Dec;34(12):1137-46
references: 22198599
references: Diabetes Care. 2004 Jan;27(1):216-22
references: 14693992
references: Diabetes. 2007 Jun;56(6):1559-68
references: 17389326
references: Diabetes. 2006 Sep;55(9):2401-11
references: 16936187
references: Eur J Cardiovasc Prev Rehabil. 2009 Aug;16(4):464-71
references: 19587603
references: Cardiology. 2009;112(4):279-86
references: 18815446
references: Exp Cell Res. 2009 Nov 1;315(18):3077-85
references: 19747911
references: J Am Coll Cardiol. 2007 Mar 13;49(10):1015-26
references: 17349880
references: Neurol Res. 2006 Jun;28(4):415-23
references: 16759444
references: Diabetes Care. 2003 Sep;26(9):2653-64
references: 12941734
references: World J Cardiol. 2010 Dec 26;2(12):411-20
references: 21191542
references: Am J Physiol Heart Circ Physiol. 2000 Jan;278(1):H233-8
references: 10644603
references: Am J Physiol Heart Circ Physiol. 2007 Jan;292(1):H1-18
references: 16980351
references: Eye (Lond). 2006 May;20(5):546-52
references: 15905870
references: Diabetes. 2008 Sep;57(9):2488-94
references: 18559661
references: Am J Physiol Cell Physiol. 2004 Sep;287(3):C572-9
references: 15308462
references: Blood. 2007 Mar 1;109(5):1801-9
references: 17053059
references: Am Heart J. 2006 Jul;152(1):190-5
references: 16824855
references: Pediatr Res. 2006 Apr;59(4 Pt 2):26R-32R
references: 16549545