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Jingfa Zhang, Qian Yang, Chaoyang Zhang, Weiye Li, Guo-Tong Xu; EPO protects BRB through down-regulating ICAM-1 and up-regulating VE-cadherin in diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5418.
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© ARVO (1962-2015); The Authors (2016-present)
To explore the effects of EPO on intercellular adhesion molecule 1 (ICAM-1) and vascular endothelial-cadherin (VE-cadherin) in diabetic rat retinas.
The Sprague-Dawley rats were rendered diabetes with intraperitoneal injection of streptozotocin. The rats were divided into 3 groups: normal control, diabetic control, and the EPO-treated diabetic rats. Intravitreal injection was performed 2 weeks or 4 months after diabetes onset. The intervention time varied from 12 hours to 7 days depending on the parameters measured. The changes of ICAM-1 and VE-cadherin were studied with western blot, real time PCR and immunofluorescence.
The protein levels of ICAM-1 were up-regulated, while VE-cadherin was down-regulated with diabetes progression from 2 weeks to 4 months. The retinal ICAM-1 expression in the diabetic group was about 1.39 (2-month diabetes, n=4, p<0.05), 1.92 (4-month diabetes, n=4, p<0.05) and 2.16 (6-month diabetes, n=4, p<0.05) folds of that in normal control. While retinal VE-cadherin expression in the diabetic group was decreased by 21.3% (2-month diabetes, n=3, p<0.05) and 21.8% (4-months diabetes, n=3, p<0.05), respectively when compared with that in normal control. After EPO treatment, the expressions of ICAM-1 and VE-cadherin could be significantly reversed at both mRNA and protein levels 4 months after diabetes onset, and its effect follows a time-dependent manner. Immunostaining result showed that ICAM-1 immunostaining was stronger in both retinal blood vessels and choriocapillaris endothelial cells (CCEs) when compared with that in normal control. And it was greatly decreased after EPO treatment.
ICAM-1 was increased, while VE-cadherin was decreased with diabetes progression. EPO maintains BRB integrity by decreasing ICAM-1 expression and increasing VE-cadherin expression in DR.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
FIG. 1 The time-dependent protein expressions of ICAM-1 and VE-cadherin from 2 weeks to 4 months after diabetes onset. N=3 in figure A and n=4 in figure B. * means p<0.05 when compared with normal control. N: normal control; D: diabetes; W: week; M: month.
FIG. 2 The mRNA (A and C) and protein (B and D) changes of ICAM-1 (A and B) and VE-cadherin (C and D) in diabetes treated with or without intravitreal injection of EPO, 4 months after diabetes. N=6 and * means p<0.05 when compared with normal control. N: normal control; D: diabetes; E: EPO (16 mU/eye).
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