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. 2021 Mar;259(3):661-671.
doi: 10.1007/s00417-020-04956-6. Epub 2020 Oct 12.

Etanercept as a TNF-alpha inhibitor depresses experimental retinal neovascularization

Yixuan Yao  1 , Yujuan Cai  2 , Ailing Sui  1 , Yiyun Yao  1 , Ting Su  1 , Yanji Zhu  1 , Bing Xie  3 , Xi Shen  4
Affiliations

Etanercept as a TNF-alpha inhibitor depresses experimental retinal neovascularization

Yixuan Yao et al. Graefes Arch Clin Exp Ophthalmol. 2021 Mar.

Abstract

Purpose: The formation of retinal neovascularization (RNV) is the primary pathological process underlying retinopathy of prematurity (ROP). Previous studies have shown that inflammatory factors are related to the formation of RNV. Tumor necrosis factor-α (TNF-α), as an important factor in the inflammatory response, is involved in the regulation of RNV formation. However, the mechanism through which TNF-α inhibition reduces RNV formation is not fully clarified. Therefore, the purpose of this study was to explore the effect of etanercept, an inhibitor of TNF-α, on RNV, and its possible mechanism.

Methods: In vivo, an oxygen-induced retinopathy (OIR) mouse model was used to determine the effect of etanercept on the formation of RNV by performing immunostaining. The effect of etanercept on tumor necrosis factor receptor-associated factor 2 (TRAF2), pro-angiogenic-related factors, and pro/anti-inflammatory factors in OIR mice was assessed by real-time PCR and Western blotting. In vitro, the effect of etanercept on TNF-α-induced human retinal microvascular endothelial cell tube formation was evaluated by tube formation assays, and the potential mechanism of etanercept was explored by Western blotting.

Results: In vivo, etanercept reduced the area of RNV and decreased the expression of TRAF2 in the OIR mouse model. Etanercept also suppressed the expression of several pro-angiogenic factors and regulated the pro/anti-inflammatory factors. In vitro, etanercept reduced endothelial cell tube formation by inhibiting activation of the NF-κB signaling pathway.

Conclusion: Etanercept can regulate pro/anti-inflammatory factors and reduce the expression of pro-angiogenic factors by inhibiting NF-κB phosphorylation, thereby reducing RNV formation.

Keywords: Etanercept; Retinal neovascularization; Tumor necrosis factor receptor-associated factor 2; Tumor necrosis factor-α.

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