June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Inflammatory manifestations of Ocular Graft versus Host Disease in the Cornea, Eyelid and Conjunctiva
Author Affiliations & Notes
  • Stephanie Duffort
    Ophthalmology, Bascom Palmer Eye Institut, Miami, FL
  • Henry Barreras
    Immunology and Microbiology, University of Miami Miller School of Medicine, Miami, FL
  • Robert Levy
    Ophthalmology, Bascom Palmer Eye Institut, Miami, FL
    Immunology and Microbiology, University of Miami Miller School of Medicine, Miami, FL
  • Victor L Perez
    Ophthalmology, Bascom Palmer Eye Institut, Miami, FL
    Immunology and Microbiology, University of Miami Miller School of Medicine, Miami, FL
  • Footnotes
    Commercial Relationships Stephanie Duffort, None; Henry Barreras, None; Robert Levy, None; Victor Perez, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 3055. doi:
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      Stephanie Duffort, Henry Barreras, Robert Levy, Victor L Perez; Inflammatory manifestations of Ocular Graft versus Host Disease in the Cornea, Eyelid and Conjunctiva. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3055.

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

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Abstract

Purpose: Graft-versus host disease (GVHD) remains a major complication of allogeneic hematopoietic stem cell transplantation (HSCT) which is frequently accompanied by ocular involvement. We previously reported that in recipient mice following experimental MHC-matched minor histocompatibility-mismatched HSCT, ocular GVHD involves the presence of donor T cells in the cornea and pathologic changes in this compartment. The present study was directed to determine the kinetics of donor allo-reactive T cell presence in the cornea and investigate the presence of macrophage infiltration into the ocular adnexal tissue in recipient mice undergoing experimental allogeneic HSCT.

Methods: Experimental HSCT Model: After high-dose TBI, C3H.SW (H2b) mice were transplanted with T cell depleted bone marrow (TCD-BM) alone from B6 (H2b) EGFP transgenic mice or allo-reactive T cells from B6 (H2b) CD45.1 transgenic mice. Recipients were monitored weekly for signs of systemic and oGVHD. In vivo fluorescent intravital microscopy was performed to track EGFP-labeled TCD-BM cells. Cornea, lids and conjunctiva were harvested weekly beginning 2 weeks post-HSCT for evaluation by histology, immunohistochemistry (IHC) and flow-cytometry.

Results: Mice transplanted with donor TCD-BM+T cells underwent weight loss and began exhibiting clinical signs of systemic GVHD. EGFP-labeled TCD-BM cells were detectable in the lid margin, conjunctiva and cornea of animals undergoing systemic GVHD by week two after transplantation and showed massive increased fluorescence by week six. Allo-reactive T cells were also present at week two which peaked at week four. IHC confirmed the presence of T cells and macrophage infiltration in the lid margin and conjunctiva. By week six, lid pathology showed significantly elevated donor inflammatory cell infiltrate consisting primarily of macrophages and T cells compared to control (TCD-BM only) recipients.

Conclusions: GVHD is a complex systemic disorder involving multiple tissues including the eye. The present study demonstrated that following HSCT, allo-reactive T cells appear first in the lid margin, conjunctiva and cornea and subsequently the recruitment of macrophages in the ocular adnexa can be identified followed by tissue damage.

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