April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Potential Effects of Toll-Like Receptor 4 Signaling on RPE Dedifferentiation by TGFβ
Author Affiliations & Notes
  • S. Horie
    Department of Ophthalmology, Tokyo Medical & Dental University, Bunkyo Ku, Japan
  • S. Sugita
    Department of Ophthalmology, Tokyo Medical & Dental University, Bunkyo Ku, Japan
  • Y. Yamada
    Department of Ophthalmology, Tokyo Medical & Dental University, Bunkyo Ku, Japan
  • M. Mochizuki
    Department of Ophthalmology, Tokyo Medical & Dental University, Bunkyo Ku, Japan
  • Footnotes
    Commercial Relationships  S. Horie, None; S. Sugita, None; Y. Yamada, None; M. Mochizuki, None.
  • Footnotes
    Support  Ministry of Education, Culture, Sports, Science and Technology, Japan: SH Grant in AID for Young Scientists (B) 21791672
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 3814. doi:https://doi.org/
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    • Get Citation

      S. Horie, S. Sugita, Y. Yamada, M. Mochizuki; Potential Effects of Toll-Like Receptor 4 Signaling on RPE Dedifferentiation by TGFβ. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3814. doi: https://doi.org/.

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

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Abstract

Purpose: : Proliferation and dedifferentiation of retinal pigment epithelial (RPE) cells known as epithelial mesenchymal transition (EMT) are associated in pathogenesis in proliferative vitreoretinopathy (PVR). TGFβ is a critical factor to induce RPE-EMT formation. Recently, it is reported that toll-like receptor (TLR) 4 signaling that acts as receptor for lipopolysaccharide (LPS) enhances TGFβ pathway. In this study, we therefore investigated the effect of TLR4 signaling on human RPE treated with TGFβ.

Methods: : ARPE-19 cell lines were used as human RPE cells, and treated with human recombinant TGFβ2 to induce RPE-EMT formation. The expressions of TLR4, TGFβ receptor (TGFβR), and TGFβ pseudoreceptor (BAMBI) on RPE were analyzed by flow cytometry or RT-PCR. The proliferation of TGFβ-treated RPE stimulated with LPS were assessed by [3H]-thymidine incorporation. Cytokine productions by RPE with LPS stimulation were also measured by cytokine beads array.

Results: : RPE-EMT formation was observed morphologically in TGFβ-treated RPE cells. TLR4 was expressed on both RPE and TGFβ-treated RPE, and the expression of TLR4 on the cells was enhanced by LPS stimulation. With stimulus by LPS, cell proliferation and IL-6 production were also enhanced in TGFβ-treated RPE. TGFβ-treated RPE exposed to LPS highly expressed TGFβR. Moreover, BAMBI transcript was downregulated in RPE exposed to LPS.

Conclusions: : TLR4 signaling promotes cell proliferation and inflammatory cytokine production of dedifferentiated RPE by TGFβ. Thus, TLR4 enhances TGFβ signaling and RPE dedifferentiation in pathogenic mechanisms of PVR.

Keywords: inflammation • retinal pigment epithelium • proliferative vitreoretinopathy 
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