Journal article
Erythropoietin protects outer blood-retinal barrier in experimental diabetic retinopathy by up-regulating ZO-1 and occludin
Clinical & experimental ophthalmology, v 47(9), pp 1182-1197
Dec 2019
PMID: 31483932
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
To explore the mechanisms of erythropoietin (EPO) in maintaining outer blood-retinal barrier (BRB) in diabetic rats.
Sprague-Dawley rats were rendered diabetic with intraperitoneal injection of streptozotocin, and then followed by intravitreal injection of EPO. Two and four weeks later, the permeability of outer BRB was examined with FITC-dextran leakage assay, following a method to demarcate the inner and outer retina based on retinal blood supply. The glyoxal-treated ARPE-19 cells, incubated with EPO, soluble EPO receptor (sEPOR), Gö6976, or digoxin, were studied for cell viability and barrier function. The expressions of ZO-1, occludin, VEGFR2, HIF-1α, MAPKs, and AKT were examined with Western blot and immunofluorescence.
The major Leakage of FITC-dextran was detected in the outer nuclear layer in both 2- and 4-week diabetic rats. The leakage was largely ameliorated in EPO-treated diabetic rats. The protein expressions of ZO-1 and occludin in the RPE-Bruch's membrane choriocapillaris complex were significantly decreased, whereas HIF-1α and JNK pathways were activated, in 4-week diabetic rats. These changes were prevented by EPO treatment. The in vitro study with ARPE-19 cells confirmed these changes, and the protective effect of EPO was abolished by sEPOR. Gö6976 and digoxin rescued the tight junction and barrier function in glyoxal-treated ARPE-19 cells.
In early diabetic rats, the outer BRB might be more severely damaged and its breakdown is the major factor for retinal oedema. EPO maintains the outer BRB integrity through down-regulation of HIF-1α and JNK signallings, and thus up-regulating ZO-1 and occludin expressions in RPE cells.
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Details
- Title
- Erythropoietin protects outer blood-retinal barrier in experimental diabetic retinopathy by up-regulating ZO-1 and occludin
- Creators
- Chaoyang Zhang - Tongji UniversityHai Xie - Tongji UniversityQian Yang - Tongji UniversityYiting Yang - Tongji UniversityWeiye Li - Tongji UniversityHaibin Tian - Tongji UniversityLixia Lu - Tongji UniversityFang Wang - Tongji UniversityJing-Ying Xu - Tongji UniversityFurong Gao - Tongji UniversityJuan Wang - Tongji UniversityCaixia Jin - Tongji UniversityGuoxu Xu - Department of Ophthalmology, The Second Affiliated Hospital of Soochow University, Suzhou, ChinaGuo-Tong Xu - Second Affiliated Hospital of Soochow UniversityJingfa Zhang - Department of Ophthalmology of Shanghai Tenth People's Hospital, Tongji Eye Institute Tongji University School of Medicine Shanghai China
- Publication Details
- Clinical & experimental ophthalmology, v 47(9), pp 1182-1197
- Publisher
- Wiley
- Grant note
- 81370999 / National Natural Science Foundation of China 2017YFA0104100 / National Key Basic Research Program of China 17ZR1431300 / Shanghai Science and Technology Committee ZJ2014-ZD-002 / Shanghai East Hospital Grant 15002150003 / Tongji University 2016YFA0101302 / National Key Basic Research Program of China 15PJ1408700 / Shanghai Pujiang Program 2015CB964601 / National Key Basic Research Program of China 81570852 / National Natural Science Foundation of China 31201084 / National Natural Science Foundation of China 18411953400 / Shanghai Science and Technology Committee
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Ophthalmology [Historical]
- Web of Science ID
- WOS:000486439200001
- Scopus ID
- 2-s2.0-85074127672
- Other Identifier
- 991019167526204721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Ophthalmology