April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
Identification of IFN as a Novel Regulator of NOD2-Mediated Uveitis
Author Affiliations & Notes
  • H. L. Rosenzweig
    Casey Eye Institute, Oregon Health & Science University, Portland, Oregon
  • T. Kawagushi
    Casey Eye Institute, Oregon Health & Science University, Portland, Oregon
  • H. Sawkar
    Casey Eye Institute, Oregon Health & Science University, Portland, Oregon
  • S. R. Planck
    Casey Eye Institute, Oregon Health & Science University, Portland, Oregon
  • T. M. Martin
    Casey Eye Institute, Oregon Health & Science University, Portland, Oregon
  • M. P. Davey
    Veterans Affairs Medical Center, Portland, Oregon
  • J. T. Rosenbaum
    Casey Eye Institute, Oregon Health & Science University, Portland, Oregon
  • Footnotes
    Commercial Relationships  H.L. Rosenzweig, None; T. Kawagushi, None; H. Sawkar, None; S.R. Planck, None; T.M. Martin, None; M.P. Davey, None; J.T. Rosenbaum, None.
  • Footnotes
    Support  This work was supported by the NEI grants F32-EY017254 and EY013093 along with Research to Prevent Blindness awards to JTR & TMM along with the CEI, and the Stan and Madelle Rosenfeld Family Trust.
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 3032. doi:
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      H. L. Rosenzweig, T. Kawagushi, H. Sawkar, S. R. Planck, T. M. Martin, M. P. Davey, J. T. Rosenbaum; Identification of IFN as a Novel Regulator of NOD2-Mediated Uveitis. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3032.

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

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Abstract

Purpose: : NOD2 (nucleotide oligomerization binding domain 2) plays an important role in innate immunity to sense muramyl dipeptide (MDP), a component of bacterial cell walls. Notably, NOD2 is linked to eye inflammation as mutations in NOD2 cause a granulomatous uveitis called Blau Syndrome. Interferon gamma (IFNγ) is known to contribute to granuloma formation. We previously reported that IFNγ-deficient mice were protected against MDP-induced ocular inflammation. Here, we explored the mechanisms by which IFNγ might contribute to inflammation induced by NOD2 activation.

Methods: : Mice deficient in NOD2 or CD11b and their wild-type controls were treated with an intravitreal injection of MDP in the presence or absence of IFNγ. The intravascular inflammatory response within the iris was quantified by intravital microscopy.

Results: : We found that IFNγ has the capacity to enhance NOD2 function in vivo as IFNγ co-treatment significantly exacerbated MDP-induced uveitis. Importantly, NOD2 deficiency abolished the synergistic effects of MDP and IFNγ indicating its essential role in this phenomenon. The potential of IFNγ to enhance inflammation required the adhesion molecule CD11b, as CD11b-deficient mice failed to show the synergistic effects from IFNγ and MDP co-treatment on adhering and infiltrating cells.

Conclusions: : In NOD2-induced uveitis, IFNγ contributes to MDP-triggered uveitis and has the capacity to further regulate NOD2 function in vivo, thereby synergizing with MDP-induced ocular inflammation. Investigation of downstream signals induced by IFNγ could provide insight into pathological mechanisms of Blau syndrome.

Keywords: inflammation • cytokines/chemokines • uveitis-clinical/animal model 
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