March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
In Vivo Imaging Of T Cell Trafficking In Eyes During Spondyloarthritis
Author Affiliations & Notes
  • Ellen J. Lee
    Casey Eye Institute, Oregon Health & Science Univ, Portland, Oregon
  • Hyun Kim
    Ophthalmology, Inje University, Pusan, Republic of Korea
  • Stephen R. Planck
    Casey Eye Institute, Oregon Health & Science Univ, Portland, Oregon
  • James T. Rosenbaum
    Casey Eye Institute, Oregon Health & Science Univ, Portland, Oregon
  • Holly L. Rosenzweig
    Casey Eye Institute, Oregon Health & Science Univ, Portland, Oregon
  • Footnotes
    Commercial Relationships  Ellen J. Lee, None; Hyun Kim, None; Stephen R. Planck, None; James T. Rosenbaum, None; Holly L. Rosenzweig, None
  • Footnotes
    Support  NIH grants EY021733, EY013093, Research to Prevent Blindness Foundation, American College of Rheumatology Research and Education Foundation
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 6900. doi:
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      Ellen J. Lee, Hyun Kim, Stephen R. Planck, James T. Rosenbaum, Holly L. Rosenzweig; In Vivo Imaging Of T Cell Trafficking In Eyes During Spondyloarthritis. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6900.

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

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Abstract

Purpose: : Uveitis, or intraocular inflammation, frequently occurs in patients with spondyloarthropathies such as ankylosing spondylitis (AS). Little is understood of the ocular component of these diseases. We previously used a murine model of spondyloarthropathy, wherein autoimmunity to a cartilage proteoglycan (PG) results in uveitis coincident with arthritis and spondylitis, to demonstrate a critical regulatory role for IFNγ in suppressing the Th17 response that contributes to uveitis in this model. Here, we focus on the in vivo T cell trafficking responses within the eye throughout the course of spondyloarthropathy in mice lacking IFNγ, wherein an exacerbated uveitis and Th17 response ensue.

Methods: : We crossed transgenic mice to yield IFNγ-deficient mice bearing DsRed2 fluorescent, PG-specific T cells. These mice were immunized i.p. with PG (n = 25 mice) or adjuvant alone (n = 4 mice). Using intravital videomicroscopy, we monitored the T cell trafficking responses within distinct eye tissues (iris, limbus, cornea) out to 6 weeks post immunization. The concurrent severity of arthritis was graded using a clinical scoring system.

Results: : Intravital videomicroscopy revealed no change in the number of T cells across all eye tissues examined in control, adjuvant-treated mice. In PG-immunized mice, increased rolling and adherence along the iris microvasculature coinciding with extravasation into the iris tissue was observed with average initial onset at ~22d, when minimal clinical arthritis was present. Despite progressive arthritis, we unexpectedly found that the presence of T cells within the iris was episodic in that it increased and regressed over a span of 7-14d. The severity and onset of the T cell response in one eye did not necessarily correspond or coincide with that of the contralateral eye. T cells preferentially accumulated in the limbus, even in control mice. In response to PG immunization, the number of T cells in the limbus was increased at 10d, which preceded their accumulation in the iris. While most of the T cells were visualized within the limbus and iris, some T cells were also detected within the cornea, wherein their presence peaked at 21d post immunization and was episodic akin to that in the iris.

Conclusions: : Our data reveal unanticipated dynamics of T cell trafficking within the eye during progressive spondyloarthritis. Investigation of T cell trafficking responses in the presence of IFNγ is underway. Future studies of how the presence of autoreactive T cells in uveitic eyes relates to disease in other target organs should be informative to multisystem diseases such as AS.

Keywords: uveitis-clinical/animal model • autoimmune disease • imaging/image analysis: non-clinical 
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