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Jingfa Zhang, Hua Xu, Lixia Lu, Haibin Tian, Weiye Li, Guo-Tong Xu; EPO protects BRB via inhibition of VEGF/VEGFR2-VE-cadherin in diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5198.
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© ARVO (1962-2015); The Authors (2016-present)
To study the protective mechanism of erythropoietin (EPO) on blood-retinal barrier (BRB) in diabetic rats
Diabetes was induced by intraperitoneal injection of streptozotocin in Sprague-Dawley rats. Four days after intravitreal injection of EPO, the retinas were harvested for detection. The primary human retinal microvascular endothelial cells (HRMECs) were treated by glyoxal with or without EPO. Transepithelial electrical resistance (TEER) was measured. The nuclear and cytoplasmic protein was extracted from HRMECs with the kit. The proteins, VEGF, VEGFR2, VE-cadherin and phospho-VE-cadherin, were detected with Western blot and immunofluorescence.
At 6-week diabetic rats, retinal VEGF and VEGFR2 proteins were significantly increased by 16.6% (n=8, P<0.01) and 21% (n=8, P<0.05), respectively, compared with that of the control; EPO down-regulated both expressions by 13.3% (n=8, P<0.05) for VEGF and 16.9% (n=8, P<0.05) for VEGFR2, respectively. Retinal VE-cadherin was gradually down-regulated with diabetes progression, which was significantly decreased by 21.3% (2-month diabetes, n=3, p<0.05) and 21.8% (4-months diabetes, n=3, p<0.05) when compared with that in normal control. EPO could significantly increased VE-cadherin expression by 20.5% (n=6, p=0.043) at 4-month of diabetes. At 2 weeks of diabetes, although EPO has no effect on VE-cadherin, it significantly reduced the ratio of phosphor-VE-cadherin to VE-cadherin. TEER measurement showed that EPO treatment could well maintain the barrier function of glyoxal-treated HRMECs. Western blot and immunofluorscence results showed that, after EPO treatment, VE-cadherin was maintained in the membrane of the HRMECs.
The present data showed that intravitreal injection of EPO could maintain BRB integrity by down-regulation of VEGF/VEGFR2-VE-cadherin in diabetic rats.
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