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


Jiajian Guo
Qingqing Yu
Genlan Yang
Wei Wei
Pengjun Tang
Ying Zheng
Fusheng Zhang
Qisheng Liu
Yujie Wang

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.


Journal Identifiers


eISSN: 1596-9827
print ISSN: 1596-5996