PMID- 33043386
OWN - NLM
STAT- MEDLINE
DCOM- 20210727
LR  - 20210727
IS  - 1435-702X (Electronic)
IS  - 0721-832X (Linking)
VI  - 259
IP  - 3
DP  - 2021 Mar
TI  - Etanercept as a TNF-alpha inhibitor depresses experimental retinal 
      neovascularization.
PG  - 661-671
LID - 10.1007/s00417-020-04956-6 [doi]
AB  - 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-alpha (TNF-alpha), as an important factor in the inflammatory 
      response, is involved in the regulation of RNV formation. However, the mechanism 
      through which TNF-alpha 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-alpha, 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-alpha-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-kappaB signaling 
      pathway. CONCLUSION: Etanercept can regulate pro/anti-inflammatory factors and 
      reduce the expression of pro-angiogenic factors by inhibiting NF-kappaB 
      phosphorylation, thereby reducing RNV formation.
FAU - Yao, Yixuan
AU  - Yao Y
AD  - Department of Ophthalmology, Ruijin Hospital, Shanghai Jiao Tong University 
      School of Medicine, 197 Ruijin Rr Road, Shanghai, 20025, China.
FAU - Cai, Yujuan
AU  - Cai Y
AD  - Department of Ophthalmology, People's Hospital of Ningxia Hui Autonomous Region, 
      Yinchuan, China.
FAU - Sui, Ailing
AU  - Sui A
AD  - Department of Ophthalmology, Ruijin Hospital, Shanghai Jiao Tong University 
      School of Medicine, 197 Ruijin Rr Road, Shanghai, 20025, China.
FAU - Yao, Yiyun
AU  - Yao Y
AD  - Department of Ophthalmology, Ruijin Hospital, Shanghai Jiao Tong University 
      School of Medicine, 197 Ruijin Rr Road, Shanghai, 20025, China.
FAU - Su, Ting
AU  - Su T
AD  - Department of Ophthalmology, Ruijin Hospital, Shanghai Jiao Tong University 
      School of Medicine, 197 Ruijin Rr Road, Shanghai, 20025, China.
FAU - Zhu, Yanji
AU  - Zhu Y
AD  - Department of Ophthalmology, Ruijin Hospital, Shanghai Jiao Tong University 
      School of Medicine, 197 Ruijin Rr Road, Shanghai, 20025, China.
FAU - Xie, Bing
AU  - Xie B
AUID- ORCID: 0000-0002-9405-635X
AD  - Department of Ophthalmology, Ruijin Hospital, Shanghai Jiao Tong University 
      School of Medicine, 197 Ruijin Rr Road, Shanghai, 20025, China. 
      brinkleybing@126.com.
FAU - Shen, Xi
AU  - Shen X
AD  - Department of Ophthalmology, Ruijin Hospital, Shanghai Jiao Tong University 
      School of Medicine, 197 Ruijin Rr Road, Shanghai, 20025, China. 
      carl_shen2005@126.com.
LA  - eng
GR  - 81570853/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20201012
PL  - Germany
TA  - Graefes Arch Clin Exp Ophthalmol
JT  - Graefe's archive for clinical and experimental ophthalmology = Albrecht von 
      Graefes Archiv fur klinische und experimentelle Ophthalmologie
JID - 8205248
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - OP401G7OJC (Etanercept)
SB  - IM
MH  - Animals
MH  - *Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
MH  - Disease Models, Animal
MH  - *Etanercept/therapeutic use
MH  - Humans
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - *Retinal Neovascularization/drug therapy
MH  - Tumor Necrosis Factor-alpha
MH  - Vascular Endothelial Growth Factor A
OTO - NOTNLM
OT  - Etanercept
OT  - Retinal neovascularization
OT  - Tumor necrosis factor receptor-associated factor 2
OT  - Tumor necrosis factor-alpha
EDAT- 2020/10/13 06:00
MHDA- 2021/07/28 06:00
CRDT- 2020/10/12 05:34
PHST- 2020/04/17 00:00 [received]
PHST- 2020/10/01 00:00 [accepted]
PHST- 2020/07/07 00:00 [revised]
PHST- 2020/10/13 06:00 [pubmed]
PHST- 2021/07/28 06:00 [medline]
PHST- 2020/10/12 05:34 [entrez]
AID - 10.1007/s00417-020-04956-6 [pii]
AID - 10.1007/s00417-020-04956-6 [doi]
PST - ppublish
SO  - Graefes Arch Clin Exp Ophthalmol. 2021 Mar;259(3):661-671. doi: 
      10.1007/s00417-020-04956-6. Epub 2020 Oct 12.