Melatonin maintains inner blood-retinal barrier via inhibition of p38/TXNIP/NF-κB pathway in diabetic retinopathy.

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.

• Authors: Lei Tang, Chaoyang Zhang, Qian Yang, Hai Xie, Dandan Liu, Haibin Tian, Lixia Lu, Jing-Ying Xu, Weiye Li, Guoxu Xu, Qinghua Qiu, Kun Liu, Dawei Luo, Guo-Tong Xu, Jingfa Zhang
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 236 Issue 8 Pg. 5848-5864 (08 2021) ISSN: 1097-4652 [Electronic] United States
• PMID: 33432588 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 Wiley Periodicals LLC.

Chemical References

• Antioxidants
• NF-kappa B
• Melatonin

Topics

• Animals
• Antioxidants (pharmacology)
• Blood-Retinal Barrier (drug effects)
• Capillary Permeability (drug effects)
• Diabetic Retinopathy (drug therapy, metabolism)
• Endothelial Cells (metabolism)
• Male
• Melatonin (pharmacology)
• NF-kappa B (drug effects, metabolism)
• Rats, Sprague-Dawley
• Retina (drug effects, metabolism)
• Retinal Vessels (drug effects)