September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
EPO protects BRB through down-regulating ICAM-1 and up-regulating VE-cadherin in diabetic retinopathy
Author Affiliations & Notes
  • Jingfa Zhang
    Department of Ophthalmology of Shanghai Tenth People’s Hospital, Tongji Eye Institute, Tongji University School of Medicine, Shanghai, China
  • Qian Yang
    Department of Ophthalmology of Shanghai Tenth People’s Hospital, Tongji Eye Institute, Tongji University School of Medicine, Shanghai, China
  • Chaoyang Zhang
    Department of Ophthalmology of Shanghai Tenth People’s Hospital, Tongji Eye Institute, Tongji University School of Medicine, Shanghai, China
  • Weiye Li
    Department of Ophthalmology, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States
  • Guo-Tong Xu
    Department of Ophthalmology of Shanghai Tenth People’s Hospital, Tongji Eye Institute, Tongji University School of Medicine, Shanghai, China
  • Footnotes
    Commercial Relationships   Jingfa Zhang, None; Qian Yang, None; Chaoyang Zhang, None; Weiye Li, None; Guo-Tong Xu, None
  • Footnotes
    Support  This work was supported by the Key State Basic Research Development Program of China (2012CBA01308 and 2013CB967501), National Natural Science Foundation of China (81570852 and 31171419), National High Technology Research and Development Program of China (2012AA020906), and Shanghai Pujiang Program (15PJ1408700).
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 5418. doi:
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    • Get Citation

      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)

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Abstract

Purpose : To explore the effects of EPO on intercellular adhesion molecule 1 (ICAM-1) and vascular endothelial-cadherin (VE-cadherin) in diabetic rat retinas.

Methods : 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.

Results : 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.

Conclusions : 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. 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).

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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