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Original Research Article | OPEN ACCESS

Neuroprotective effects of etanercept on diabetic retinopathy via regulation of the TNF-α/NF-κB signaling pathway

Jiajian Guo1, Qingqing Yu2, Genlan Yang1, Wei Wei3, Pengjun Tang1, Ying Zheng2, Fusheng Zhang1, Qisheng Liu1, Yujie Wang4

1Venus Eye Hospital, Ganzhou, China; 2The 903rd Hospital of the Joint Logistics Support Force of PLA, Hangzhou, China; 3Department of Ophthalmology, Armed Police Force First Mobile Corps Hospital, Dingzhou, China; 4Department of Ophthalmology, Zhuji people's Hospital of Zhejiang Province, Zhuji, China.

For correspondence:-  Yujie Wang   Email: 1303572621@qq.com

Accepted: 27 September 2022        Published: 28 October 2022

Citation: Guo J, Yu Q, Yang G, Wei W, Tang P, Zheng Y, et al. Neuroprotective effects of etanercept on diabetic retinopathy via regulation of the TNF-α/NF-κB signaling pathway. Trop J Pharm Res 2022; 21(10):2077-2083 doi: 10.4314/tjpr.v21i10.6

© 2022 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To study the influence of etanercept on diabetic retinopathy in rats via tumor necrosis factor alpha (TNF-α)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway.
Methods: Thirty-six Sprague-Dawley (SD) rats were randomly divided into normal, model and etanercept groups. The expression of Caspase-3 was determined by immunohistochemistry, while the relative protein and mRNA expression levels of TNF-α and NF-κB were determined by Western blotting and quantitative polymerase chain reaction, respectively. Besides, the contents of TNF-α and interleukin-1 beta (IL-1β) were evaluated using enzyme-linked immunosorbent assay (ELISA), while cell apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL).
Results: Immunohistochemical studies showed that the mean optical density of tissues positive for caspase-3 in both the model and etanercept groups were significantly higher than in the normal group (p < 0.05), while the mean optical density in the etanercept group was significantly lower than that in the model group (p < 0.05). The protein expression levels of TNF-α and NF-κB in the etanercept group were significantly lower than those in the model group (p < 0.05). Furthermore, mRNA expressions of TNF-α and NF-κB declined in the etanercept group (p < 0.05); in addition, TNF-α, and IL-1β levels in the etanercept group were lower than in the model group (p < 0.05). Cell apoptosis in the etanercept group was also lower than in the model group.
Conclusion: Etanercept suppresses TNF-α/NF-κB signaling pathway thereby repressing inflammation and cell apoptosis in diabetic retinopathy rats. Therefore, etenercept’s neuroprotective effect may potentially be useful in developing a suitable therapy for diabetic neuropathy.

Keywords: Diabetic retinopathy, Etanercept, TNF-α/NF-κB signaling pathway, Inflammation, Apoptosis

Impact Factor
Thompson Reuters (ISI): 0.6 (2023)
H-5 index (Google Scholar): 49 (2023)

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