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Samantha Herretes, Antonia M. Mueller, Stephanie Duffort, Maitee Urbieta, Jose Echegaray, Robert Levy, Victor L. Perez; Corneal Changes in a Pre-Clinical Murine Model of Chronic Graft-versus-Host Disease. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1119.
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Graft-versus-host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell (HSC) transplantation. Severe dry eye is frequently present in patients with chronic GVHD, and can be a potentially blinding condition. Several studies have evaluated ocular affectation in experimental transplants across a full MHC-mismatch during acute GVHD. In the present study, we investigated corneal inflammatory changes in a clinically relevant mouse model of chronic GVHD.
Lethally irradiated BALB.B mice were infused with C57BL6 HSC with or without T cell subsets, or together with whole splenocytes (WS). Corneal inflammatory changes were histologically evaluated at 12 or 18 months using a scale ranging from 0 to 9 points based on 5 parameters: thickness, presence of blood vessels, inflammatory cell infiltrate, and keratinization.
In contrast to mice receiving HSC only, 12 out of 13 animals given T cells with the graft revealed corneal involvement. Recipients of CD4+CD8 T cells exhibited more severe corneal thickening, inflammatory cell infiltrates, neovascularization, and keratinization compared with recipients of CD4 or CD8 T cells alone (scores of 7.25±1.5 vs. 4.5±0.7 and 3.25±2.75, respectively). While all groups trended higher scores than HSC alone, due to limited sample size, only the CD4+CD8 group reached statistical significance (one-way ANOVA p<0.05) at this time. Notably, the level of corneal manifestations present correlated with the severity of skin lesions associated with chronic GVHD observed in these animals.
We describe corneal involvement in a clinically relevant model of chronic GVHD, which should help to elucidate the pathophysiology of ocular GVHD. Additionally, the findings confirm the role of T cell mediated ocular surface inflammation and may potentially represent a new mouse model of dry eye.
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