Wei Zhang1, Hua Yan. 1. Department of Ophthalmology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Tianjin 300052, China.
Abstract
PURPOSE: 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.
PURPOSE: 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.
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