June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Evaluating clinical severity of Ocular Graft vs Host Disease in Three Murine Models using a Novel Scoring System
Author Affiliations & Notes
  • Seema Sajjan
    University of Maryland School of Medicine, Baltimore, Maryland, United States
  • Ellis Tibbs
    University of Maryland School of Medicine, Baltimore, Maryland, United States
  • Long Wu
    University of Maryland School of Medicine, Baltimore, Maryland, United States
  • Sarah Sunshine
    University of Maryland School of Medicine, Baltimore, Maryland, United States
  • Xuefang Cao
    University of Maryland School of Medicine, Baltimore, Maryland, United States
  • Footnotes
    Commercial Relationships   Seema Sajjan None; Ellis Tibbs None; Long Wu None; Sarah Sunshine None; Xuefang Cao None
  • Footnotes
    Support  CRF
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 4415 – F0094. doi:
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      Seema Sajjan, Ellis Tibbs, Long Wu, Sarah Sunshine, Xuefang Cao; Evaluating clinical severity of Ocular Graft vs Host Disease in Three Murine Models using a Novel Scoring System. Invest. Ophthalmol. Vis. Sci. 2022;63(7):4415 – F0094.

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

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Abstract

Purpose : Development of mouse models and corresponding grading systems is imperative to studying the pathophysiology of human disease. Ocular graft versus host disease (oGvHD) affects 40-60% of patients after allogeneic hematopoietic stem cell transplant (HSCT) characterized by decreased vision, pain, fibrosis, and severe dry eye disease. We have developed a novel grading scale for murine models of oGvHD and tested it in three oGvHD murine models.

Methods : We evaluated 3 different murine models of oGVHD (N=5/group), including major histocompatability (MHC) mismatched (C57Bl/6 donor and Balbc/J host), haploidentical (C57Bl/6 donor and B6D2F1 host), and MHC matched but minor histocompatibility antigen-mismatched (129 donor and C57Bl/6 host). Mice underwent total body irradiation followed by donor T and B cell depleted bone marrow +/- splenocyte from donor mice injected via tail vein at day 1 post radiation. The control mice did not receive splenocytes. GvHD and oGvHD scoring was performed weekly. The novel grading system consisted of categories such as eyelid changes (erythema and edema), periocular fur loss, corneal clarity (corneal haze and visualization of intraocular structures), and corneal fluorescein staining (punctate keratopathy and ulceration) with a grade of 0 (normal) to 3 or 4 (most severe) in each category. The overall score for oGvHD at each time-point is the individual scores for each category per mouse summed and then averaged within the groups.

Results : The MHC mismatched mice experienced higher oGvHD score as compared to the control at days 8, 14, 22, 28 and 42 were p= <0.0001 at all timepoints. The haploidentical mice oGvHD score as compared to control at days 6, 13, 19 and 26 were p= 0.20, p= 0.47, p= 0.051, and p= 0.01, respectively. In the MHC matched but minor histocompatibility antigen-mismatched mice, the oGvHD score as compared to the control at days 6, 13, 19, and 26 were p= 0.49, p= 0.n09, p= 0.06, and p= 0.69, respectively.

Conclusions : This is the first study to directly compare and evaluate the timing and severity of 3 different murine models of oGVHD. Utilizing our novel grading system, we identified clinically significant differences between the splenocyte treated and control groups in all 3 models of oGVHD, ultimately enabling us to use varying genetic backgrounds and treatment modalities to find novel targets for oGVHD.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

 

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