May 2006
Volume 47, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2006
Poly(I:C)–Induced Corneal Inflammation is Exacerbated in the Absence of Functional MyD88 Expression
Author Affiliations & Notes
  • A.C. Johnson
    Ophthalmology, Case Western Reserve Univ, Cleveland, OH
  • Y. Sun
    Ophthalmology, Case Western Reserve Univ, Cleveland, OH
  • J.H. Lass
    Ophthalmology, Case Western Reserve Univ, Cleveland, OH
  • E. Pearlman
    Ophthalmology, Case Western Reserve Univ, Cleveland, OH
  • Footnotes
    Commercial Relationships  A.C. Johnson, None; Y. Sun, None; J.H. Lass, None; E. Pearlman, None.
  • Footnotes
    Support  NIH Grant EY14362; the Research to Prevent Blindness Foundation; the Ohio Lions Eye Research Foundation; and T32 EY07157
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 4371. doi:
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      A.C. Johnson, Y. Sun, J.H. Lass, E. Pearlman; Poly(I:C)–Induced Corneal Inflammation is Exacerbated in the Absence of Functional MyD88 Expression . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4371.

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

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Abstract

Purpose: : Toll–like receptors (TLRs) play a critical role in innate immune responses through the recognition of a variety of microbial products. Human corneal epithelium expresses TLR2, TLR3, TLR4 and TLR5; and activation of TLR2, TLR4, and TLR9 within the murine corneal epithelium induces neutrophil infiltration in the corneal stroma and the development of keratitis. Furthermore, keratitis in these mouse models was demonstrated to be critically dependent upon the expression of MyD88. While many TLRs signal through MyD88, TLR3 and a subset of TLR4 activation events are known to signal through a MyD88–independent pathway, involving the adaptor molecule TRIF [TIR domain–containing adaptor inducing IFN–ß]. To this end, current studies have endeavored to determine the presence and possible role of a MyD88–independent pathway of corneal inflammation.

Methods: : In vivo studies were performed with C57BL/6 and MyD88–/– mice. Corneal epithelium was abraded and treated with Pam3Cys (TLR2), LPS (TLR4), and Poly(I:C) (TLR3), and chemokine production, development of stromal haze, and neutrophil and F4/80+ cell infiltration were measured.

Results: : In vivo mouse experiments demonstrated that Poly(I:C)–induced inflammation (stromal haze, neutrophil infiltration, and F4/80+ cell infiltration) is delayed when compared with TLR2 and TLR4 induced responses in C57BL/6 mice. Furthermore, the observed responses were exacerbated in MyD88–/– mice when compared to littermate control animals. Mouse corneal epithelium also produced CCL5 / RANTES after stimulation with Poly(I:C), consistent with a MyD88 – independent response .

Conclusions: : These findings demonstrate that Poly(I:C) induces significant levels of inflammation in the murine cornea and that this inflammation occurs independently of MyD88 expression. Furthermore, MyD88 may be playing a regulatory role on the TLR3 activation pathway, a link that has not been previously observed.

Keywords: cornea: epithelium • keratitis • inflammation 
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