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Stella K. Kim, Janhavi Modak, Neera Singh, Clifton Stephens, Steven Kornblau; Murine Model of Ocular Graft Vs. Host Disease. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2936.
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© ARVO (1962-2015); The Authors (2016-present)
To describe a murine model of ocular graft vs. host disease
MHC matched transplantation was performed using AKR/J as recipients with B10 as donor mice. AKR/J mice were irradiated with 9 Gy and a cohort (Group B, n=24) was given bone marrow cells and another cohort (Group C, n=24) with bone marrow cells plus lymphocytes, from B10 mice. The mice were graded every other day with murine GVHD scoring system (Ferrera et al.). External examination, Schirmer’s tests were performed, and tissues were harvested at each time point. Histology was graded (1-4 severity scale) for ocular structures and skin, GI tract, liver typically affected by GVHD. T-test, Mann-Whitney, linear regression, and Pearson correlation coefficient analysis were used for statistics.
The animal age, weight, and tear function tests between all groups were comparable pre-transplantation. Group A (radiation control) died in 10-14 days. After transplantation, group B and C showed a statistically significant difference in the GVHD scores (p< 0.001). All mice with GVHD showed clinical features of ocular GVHD in varying degree (thickened erythematous blepharitis, hyperkerotosis, lid margin ulcerations). There was a statistically significant decrease in the Schirmer’s score without anesthesia at wk 2, 4, 6 between B and C (p= 0.005, p= 0.014, p= 0.016). There was a high negative correlation of GVHD score to Schirmer scores (with and without anesthesia) for both groups. Both B and C showed histological changes that are hallmark of GVHD (apoptosis of tissues, including the lid, conjunctiva, lacrimal gland, meibomian gland, as well as in the skin, GI track and liver changes). There was a statistically significant difference between group B and C in histology severity scores in the eye lids and skin (p=0.029, p=0.001 respectively) and a positive correlation of lid and meibomian gland histology severity to GVHD systemic scores in C. Conjunctiva, lid, and skin histology showed statistically significant positive correlation to systemic GVHD score in both B and C, and while there was a weak correlation in other tissues, these were not statistically significant.
Murine model of ocular GVHD is described using AKR/J as recipient and B10 as donor mice. Basal tear function appears to be affected for both transplanted group but more in the mice with higher GVHD scores. Histology evaluation shows GVHD changes in ocular structures, including the lid, lacrimal gland, conjunctiva, and cornea. Further study is ongoing to establish the inflammatory milieu of the murine ocular GVHD.
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