June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Infliximab Attenuates Tumor Necrosis Factor-α-Induced Alterations in Non-Pigmented Ciliary Epithelium
Author Affiliations & Notes
  • Hiroshi Yamada
    Ophthalmology, Aichi Medical University, Nagakute, Japan
  • Masahiko Yoneda
    Biochemistry and Molecular Biology, School of Nursing and Health, Aichi Prefectural University, Nagoya, Japan
  • Shingo Inaguma
    Pathology, Aichi Medical University, Nagakute, Japan
  • Masayoshi Iwaki
    Ophthalmology, Aichi Medical University, Nagakute, Japan
  • Masahiro Zako
    Ophthalmology, Aichi Medical University, Nagakute, Japan
  • Footnotes
    Commercial Relationships Hiroshi Yamada, None; Masahiko Yoneda, None; Shingo Inaguma, None; Masayoshi Iwaki, None; Masahiro Zako, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 115. doi:
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      Hiroshi Yamada, Masahiko Yoneda, Shingo Inaguma, Masayoshi Iwaki, Masahiro Zako; Infliximab Attenuates Tumor Necrosis Factor-α-Induced Alterations in Non-Pigmented Ciliary Epithelium. Invest. Ophthalmol. Vis. Sci. 2013;54(15):115.

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Abstract

Purpose: In human non-pigmented ciliary epithelial cells (HNPCECs) in vitro, we investigated changes in the mRNA and protein expression levels of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in the presence of tumor necrosis factor-alpha (TNF-α), and examined the effects of infliximab addition. Degradation of claudin-1 and occludin, and permeability changes in HNPCECs were also evaluated.

Methods: HNPCECs were cultured in the presence or absence of TNF-α, and TNF-α-exposed cells were treated with or without infliximab. We measured the expression levels of MMP-1, MMP-2, MMP-3, MMP-9, TIMP-1, and TIMP-2 in HNPCECs by real-time polymerase chain reaction and by enzyme-linked immunosorbent assay. HNPCECs and swine ciliary body were treated with MMPs, and immunostained. Permeability of MMP-treated-HNPCECs was measured using a cell-based permeability assay.

Results: The expressions of MMP-1, MMP-3, and MMP-9 increased in the presence of 10 ng/mL TNF-α, and these altered expression levels were reversed by the addition of infliximab. Immunostaining showed that MMP-1, MMP-3, and MMP-9 degraded claudin-1 and occludin, after which significant increases in HNPCEC permeability were detected.

Conclusions: TNF-α increased the expressions of MMPs in cells comprising the blood-aqueous barrier (BAB). Components of the tight junctions of the BAB were degraded by MMPs, which increased permeability through the cells. Infliximab was effective at attenuating the TNF-α-induced increases in MMP expressions in cells comprising the BAB, suggesting that such treatment may clinically prevent anterior uveitis.

Keywords: 746 uveitis-clinical/animal model • 557 inflammation  
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