June 2020
Volume 61, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2020
Inhibition of ACHE Attenuated Retinal Inflammation via Suppressing NF-κB Activation
Author Affiliations & Notes
  • Jingming Li
    Department of Ophthalmology, First Affiliated Hospital of Xi'an Jiaotong University, China
  • Yingying Chen
    Department of Ophthalmology, Hainan People’s Hospital, China
  • Xian Zhang
    Affiliated Eye Hospital of Nanchang University, China
  • Qian Chen
    Xiamen Eye Institute, China
  • Qiuping Liu
    Affiliated Eye Hospital of Nanchang University, China
  • Footnotes
    Commercial Relationships   Jingming Li, None; Yingying Chen, None; Xian Zhang, None; Qian Chen, None; Qiuping Liu, None
  • Footnotes
    Support  NSFC Grants 81960177, 81740158, 81400427, 81460163, 81300786 and 31801195; Young Talent Scholar Grant 2016KJXX-12; FRFCU Grant xjj2015015; RFDP grant 20133601120012; Research Grants from Jiangxi Education Department GJJ14094, GJJ13175; Research Grants from Jiangxi Science and Technology Department 20192BAB205049, 20142BDH80005, 20142BAB215029, 20132BAB205024.
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 1321. doi:
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    • Get Citation

      Jingming Li, Yingying Chen, Xian Zhang, Qian Chen, Qiuping Liu; Inhibition of ACHE Attenuated Retinal Inflammation via Suppressing NF-κB Activation. Invest. Ophthalmol. Vis. Sci. 2020;61(7):1321.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Elevated inflammatory cytokines contribute to the pathogenesis of various retinal diseases such as diabetic retinopathy, retinal vasculitis and et al. However, the underlying mechanism remains largely unknown. Recent studies demonstrated that ACHE is an inflammatory indicator in central neural system. This study was aimed to dissect the role of ACHE in retinal inflammation, and its mechanism of action.

Methods : Retinal inflammation was induced by intravitreal injection of tumor necrosis factor-α (TNF-α) in heterozygous ACHE knockout mice (ACHE+/-) and wild type mice (ACHE+/+). Donepezil, a well-known ACHE inhibitor, was administrated by daily gavage. Expression of ACHE and intercellular adherent molecule-1 (ICAM-1), infiltration of CD11b+ inflammatory cells, retinal leukostasis and vascular leakage was determined in both ACHE+/- and ACHE+/+ mice. ARPE-19 cells, a human retinal pigment epithelial cell line, were cultured for in vitro assay. Knockdown of ACHE was achieved by lipofectamine-mediated siRNA transfection and pharmaceutical suppression of ACHE was manipulated by donepezil. Cellular expression and distribution of ACHE, ICAM-1, and phosphorylation of NF-κB, IκB and IKKα/β were detected by western-blot analysis or immunocytochemistry.

Results : Retinal expression of ACHE was dramatically upregulated, in parallel with increased ICAM-1 expression, enhanced leukostasis and augmented CD11b+ inflammatory cells infiltration as well as vascular hyperpermeability in ACHE+/+ mice injected with TNF-α. However, TNF-α-injected ACHE+/- mice showed lower level of ICAM-1, less leukostasis and fewer infiltrated CD11b+ cells. Moreover, TNF-α-induced retinal vascular leakage was significantly reduced in ACHE+/- mice. Similarly, TNF-α-induced retinal inflammatory response were also attenuated by donepezil intervention. In addition, TNF-α treatment resulted in significant induction of ACHE, upregulation of ICAM-1 and nuclear translocation of NF-κB in cultured-ARPE-19 cells. Genetic and pharmaceutical suppression of ACHE markedly attenuated TNF-α-induced ICAM-1 expression. Meanwhile, inhibition of ACHE reduced TNF-α-induced phosphorylation of NF-κB, IκB and IKKα/β in ARPE-19 cells.

Conclusions : The present study reveals a pivotal role of ACHE in retinal inflammation. Inhibition of ACHE attenuates retinal inflammation and retinal leakage likely through suppressing NF-κB signaling activation.

This is a 2020 ARVO Annual Meeting abstract.

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