April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Pre-Clinical and Clinical Inflammation of Ocular Adnexa in Graft-versus-Host Disease
Author Affiliations & Notes
  • Samantha Herretes
    Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL
  • Juan Carlos Murillo
    Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL
  • Stephanie Duffort
    Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL
  • Carolina Betancurt
    Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL
  • Zaina Al-Mohtaseb
    Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL
  • Tayyeba Ali
    Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL
  • Daniel Waren
    Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL
  • Henry Barreras
    Immunology and Microbiology, University of Miami Miller School of Medicine, Miami, FL
  • Robert Levy
    Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL
    Immunology and Microbiology, University of Miami Miller School of Medicine, Miami, FL
  • Victor L Perez
    Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL
    Immunology and Microbiology, University of Miami Miller School of Medicine, Miami, FL
  • Footnotes
    Commercial Relationships Samantha Herretes, None; Juan Murillo, None; Stephanie Duffort, None; Carolina Betancurt, None; Zaina Al-Mohtaseb, None; Tayyeba Ali, None; Daniel Waren, None; Henry Barreras, None; Robert Levy, None; Victor Perez, Allergan (C)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 2773. doi:
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      Samantha Herretes, Juan Carlos Murillo, Stephanie Duffort, Carolina Betancurt, Zaina Al-Mohtaseb, Tayyeba Ali, Daniel Waren, Henry Barreras, Robert Levy, Victor L Perez; Pre-Clinical and Clinical Inflammation of Ocular Adnexa in Graft-versus-Host Disease. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2773.

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

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Abstract

Purpose: Graft-versus host disease (GVHD) occurs frequently after hematopoietic stem cell transplantation (HSCT), and is induced by allo-reactive T cells. Ocular GVHD (oGVHD) is a potentially blinding condition that may range from mild to severe, affecting the cornea and ocular adnexa, including lacrimal glands (LG), meibomian glands (MG), and conjunctiva. Our objective was to examine ocular adnexal tissue obtained from recipient mice undergoing experimental MHC-matched HSCT, while concomitantly performing clinical assessment of the ocular adnexa in patients following T cell replete 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 or BM+T cells from either wild type B6 (H2b) or EGFP transgenic mice, which express green fluorescent protein in all cells. Recipients were monitored weekly for signs of systemic and oGVHD. Lids and LG were harvested at ~2months for evaluation by histology, immunohistochemistry and flow cytometry. / Clinical HSCT: patient symptoms were evaluated by the ocular surface disease index (OSDI), LG function was assessed by measurement of tear production (Schirmer I), and presence of MG dysfunction (MGD) was appraised by a lid scoring system.

Results: Experimental HSCT Model: mice begin to develop systemic and oGVHD ~weeks 3 and 6 respectively. Animals with GVHD showed increased lid fluorescence in vivo (increased donor GFP+ inflammatory cells in the lid margin). LG and lid pathology showed significantly elevated donor inflammatory cell infiltrate consisting primarily of macrophages and T cells compared to control (TCD-BM only) recipients (P>0.05). / Clinical HSCT: patients exhibited dry eye symptoms evidenced by elevated OSDI scores. Aqueous deficiency due to LG dysfunction was revealed by decreased tear fluid production. MGD was evidenced by high scores in the lid evaluation.

Conclusions: Donor T cells are critical for the production of oGVHD and infiltration of ocular adnexal tissues, specifically LG and lids. As far as we are aware, this is the initial report of an animal model demonstrating lid inflammation in oGVHD. Together with the clinical observations of aqueous deficiency and MGD, we speculate that this MHC-matched experimental HSCT model may be reflective of adnexal complications observed in clinical HSCT recipients.

Keywords: 480 cornea: basic science • 479 cornea: clinical science • 555 immunomodulation/immunoregulation  
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