Etanercept as a TNF-alpha inhibitor depresses experimental retinal neovascularization
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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 1
&
Xi Shen 1
Received: 17 April 2020 / Revised: 7 July 2020 / Accepted: 1 October 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
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 receptorassociated 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
Key Messages What was known before It is known that TNF- and VEGF are involved in the formation of retinal neovascularization. What this study adds Etanercept can inhibit retinal neovascularization in oxygen-induced retinopathy mouse model. Etanercept suppresses retinal neovascularization by inhibiting NF- κB phosphorylation rather than through VEGFR1, VEGFR2, and ERK signaling pathways.
Yixuan Yao and Cai Yujuan contributed equally to the work presented here and should therefore be regarded as equivalent authors. * Bing Xie [email protected] * Xi Shen [email protected]
1
Department of Ophthalmology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Rr Road, Shanghai 20025, China
2
Department of Ophthalmology, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan, China
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