Journal article
Melatonin maintains inner blood-retinal barrier via inhibition of p38/TXNIP/NF-kappa B pathway in diabetic retinopathy
Journal of cellular physiology, v 236(8), pp 5848-5864
01 Aug 2021
PMID: 33432588
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The pathophysiology of diabetic retinopathy (DR) was complex. Under hyperglycemic conditions, the release of proinflammatory cytokines and the adhesion of leukocytes to retinal capillaries contribute to endothelial damage and the subsequent increase in vascular permeability resulting in macular edema. Melatonin, produced in the retina to regulate redox reactions and dopamine metabolism, plays protective roles against inflammation and oxidative stress. Considering its anti-inflammatory and antioxidative properties, melatonin was speculated to exert beneficial effects in DR. In this study, we characterized the protective effects of melatonin on the inner blood-retinal barrier (iBRB), as well as the possible mechanisms in experimental DR. Results showed that in diabetic rat retinas, the leakage of iBRB and the expression of inflammatory factors (VEGF, TNF-alpha, IL-1 beta, ICAM-1, and MMP9) increased dramatically, while the expression of tight junction proteins (ZO-1, occludin, JAM-A, and claudin-5) decreased significantly. The above changes were largely ameliorated by melatonin. The in vivo data were confirmed in vitro. In addition, the protein expressions of p38 MAPK, NF-kappa B, and TXNIP were upregulated significantly in diabetes and were downregulated following melatonin treatment. Melatonin could maintain the iBRB integrity by upregulating the expression of tight junction proteins via inhibiting p38/TXNIP/NF-kappa B pathway, thus decreasing the production of inflammatory factors. This study may shed light on the development of melatonin-based DR therapy.
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Details
- Title
- Melatonin maintains inner blood-retinal barrier via inhibition of p38/TXNIP/NF-kappa B pathway in diabetic retinopathy
- Creators
- Lei Tang - Tongji UniversityChaoyang Zhang - Shanghai First People's HospitalQian Yang - Tongji UniversityHai Xie - Tongji UniversityDandan Liu - Tongji UniversityHaibin Tian - Tongji UniversityLixia Lu - Tongji UniversityJing-Ying Xu - Tongji UniversityWeiye Li - Tongji UniversityGuoxu Xu - Soochow Univ, Dept Ophthalmol, Affiliated Hosp 2, Suzhou, Peoples R ChinaQinghua Qiu - Shanghai First People's HospitalKun Liu - Shanghai First People's HospitalDawei Luo - Shanghai First People's HospitalGuo-Tong Xu - Second Affiliated Hospital of Soochow UniversityJingfa Zhang - Shanghai First People's Hospital
- Publication Details
- Journal of cellular physiology, v 236(8), pp 5848-5864
- Publisher
- Wiley
- Number of pages
- 17
- Grant note
- 2017YFA0104100 / National Key Basic Research Program of China; National Basic Research Program of China 81570852; 81870667; 81970810; 81970811 / National Natural Science Foundation of China; National Natural Science Foundation of China (NSFC) 15PJ1408700 / Shanghai Pujiang Program 2019ZX09301113 / National Major Scientific and Technological Special Project for "Significant New Drugs Development" 17ZR1431300; 18411953400; 19495800700 / Science and Technology Commission of Shanghai Municipality; Science & Technology Commission of Shanghai Municipality (STCSM)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Ophthalmology [Historical]
- Web of Science ID
- WOS:000606783500001
- Scopus ID
- 2-s2.0-85099242210
- Other Identifier
- 991019167517404721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Cell Biology
- Physiology