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Melatonin maintains inner blood‐retinal barrier via inhibition of p38/TXNIP/NF‐κB pathway in diabetic retinopathy
- Source :
- Journal of Cellular Physiology. 236:5848-5864
- Publication Year :
- 2021
- Publisher :
- Wiley, 2021.
-
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-α, IL-1β, 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-κB, 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-κB pathway, thus decreasing the production of inflammatory factors. This study may shed light on the development of melatonin-based DR therapy.
- Subjects :
- Male
0301 basic medicine
medicine.medical_specialty
Physiology
Clinical Biochemistry
Blood–retinal barrier
Inflammation
Vascular permeability
Occludin
medicine.disease_cause
Antioxidants
Retina
Proinflammatory cytokine
Capillary Permeability
Rats, Sprague-Dawley
Melatonin
03 medical and health sciences
0302 clinical medicine
Internal medicine
Blood-Retinal Barrier
medicine
Animals
Diabetic Retinopathy
Chemistry
NF-kappa B
Endothelial Cells
Retinal Vessels
Cell Biology
030104 developmental biology
Endocrinology
medicine.anatomical_structure
030220 oncology & carcinogenesis
medicine.symptom
Oxidative stress
TXNIP
medicine.drug
Subjects
Details
- ISSN :
- 10974652 and 00219541
- Volume :
- 236
- Database :
- OpenAIRE
- Journal :
- Journal of Cellular Physiology
- Accession number :
- edsair.doi.dedup.....925bbb5e06246be03fc48a7ea0cb80af