April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Non-self extracellular DNA (eDNA) may potentiate inflammation and severity of dry eyes in patients with chronic ocular Graft-Versus-Host Disease (GVHD)
Author Affiliations & Notes
  • Sapna Tibrewal
    Corneal Neurobiology Laboratory, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL
  • Joy Sarkar
    Corneal Neurobiology Laboratory, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL
  • Sarmad Hassan Jassim
    Corneal Neurobiology Laboratory, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL
  • Yair Ivanir
    Corneal Neurobiology Laboratory, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL
  • Eunjae Kim
    Corneal Neurobiology Laboratory, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL
  • Yong Soo Byun
    Corneal Neurobiology Laboratory, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL
  • Rama Wahood
    Corneal Neurobiology Laboratory, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL
  • Shweta Chaudhary
    Corneal Neurobiology Laboratory, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL
  • Kaele Leonard
    Corneal Neurobiology Laboratory, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL
  • Sandeep Jain
    Corneal Neurobiology Laboratory, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL
  • Footnotes
    Commercial Relationships Sapna Tibrewal, None; Joy Sarkar, None; Sarmad Jassim, None; Yair Ivanir, None; Eunjae Kim, None; Yong Soo Byun, None; Rama Wahood, None; Shweta Chaudhary, None; Kaele Leonard, None; Sandeep Jain, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 2008. doi:https://doi.org/
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      Sapna Tibrewal, Joy Sarkar, Sarmad Hassan Jassim, Yair Ivanir, Eunjae Kim, Yong Soo Byun, Rama Wahood, Shweta Chaudhary, Kaele Leonard, Sandeep Jain; Non-self extracellular DNA (eDNA) may potentiate inflammation and severity of dry eyes in patients with chronic ocular Graft-Versus-Host Disease (GVHD). Invest. Ophthalmol. Vis. Sci. 2014;55(13):2008. doi: https://doi.org/.

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

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Abstract

Purpose: We hypothesize that donor neutrophil-derived non-self eDNA present on the ocular surface of patients with chronic ocular GVHD promotes inflammation and severity of dry eye.

Methods: We examined patients with severe dry eye disease (Schirmer I ≤ 2 mm) and compared the clinical signs and symptoms between GVHD (n=12) and Non-GVHD (n=12) dry eye patients. Fluorescent in situ hybridization (FISH) was performed to identify the sex chromosomes in mucoid films seen on the ocular surface of these patients. One-way Mixed Lymphocyte Reaction (MLR) was performed using stimulator cells (irradiated C57BL/6 mouse splenocytes) and responder cells (BALB/c mouse splenocytes) to evaluate differences in immunogenic potential of allogeneic (C57BL/6 mouse) and syngeneic (BALB /c mouse) DNA. Cell-cytotoxicity experiments were performed using two different human corneal epithelial cell lines (Human corneal epithelial Large T antigen; HCET, and Human corneolimbal epithelial; HCLE) to compare the effect of allogeneic (HCLE) and syngeneic (HCET) DNA on cell viability, cytotoxicity and cellular apoptosis.

Results: GVHD patients were more symptomatic than Non-GVHD dry eye patients with similar tear deficiency (Schirmer I = 0.5±0.2 and 0.7±0.2 mm, respectively, p=0.16; OSDI score = 54.7±4.6 and 41.8±3.8, respectively, p<0.05). Mucoid films from ocular surface of GVHD patients contained abundant neutrophil extracellular traps (NETs). FISH examination revealed that eDNA within these NETs was non-self. Syngeneic and allogeneic DNA did not produce cytotoxicity, cell viability, or apoptosis in HCET cells, however allogeneic DNA was significantly more immunostimulatory than syngeneic DNA in MLR.

Conclusions: Patients with chronic GVHD have non-self eDNA on the ocular surface, which has greater immunostimulatory potential than self DNA. This may be one reason for greater severity of dry eye disease in these patients.

Keywords: 479 cornea: clinical science • 486 cornea: tears/tear film/dry eye  
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