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Michael E Stern, Katherine S Held, Chris S Schaumburg, Euikyon Oh, Sveti Ugarte, Larry A Wheeler, Margarita Calonge, Jerry Y Niederkorn, Stephen C Pflugfelder; Stress-Induced Damage to the Ocular Surface Resembling Dry Eye can Occur Independently of Chronic T cell-mediated Disease. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3059.
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CD4+ T cells make a significant contribution to chronic inflammation during the immunopathogenesis of Dry Eye. To begin to understand the contribution of T cell-independent mechanisms of disease, T cell deficient RAG1-/- mice were exposed to desiccating stress (DS), and evaluated for abnormalities in corneal epithelial cells, proinflammatory cytokine expression and inflammatory cell infiltration over a 16 day exposure.
Dry Eye disease was induced by exposing female RAG1-/- mice to desiccating stress (DS: subcutaneous scopolamine, 0.1mg/day; humidity 20%; sustained airflow). Mice were evaluated for corneal fluorescein staining, and ocular surface tissues and tears were collected for analysis at various time points. Immunohistochemistry was used to evaluate neutrophil and monocyte infiltration at 0, 3, 6 and 16 days of DS.
RAG1-/- mice exposed to DS displayed a significant increase (p≤0.001) in corneal fluorescein staining on Days 3, 6, 10 and 16 days DS. Immunohistochemistry revealed a significant (p≤0.001) increase in neutrophils in the conjunctiva at Day 6 (7.9±1.2), Day 10 (8.5±1.4) and Day 16 (10.2±2.1) in RAG1-/- mice exposed to DS compared to naïve mice (2.1±0.4). A similar trend was observed for increased CD11b+ cells in the conjunctiva at Day 6 (34.5±5.7; p≤0.05), Day 10 (40.3±4.5; p≤0.01) and Day 16 (46.3 ±3.7; p≤0.001) in DS mice relative to naïve mice (23.1±3.4). A significant (p≤0.05) increase in CD11b+ cells was also observed in the cornea at Day 16 (16.3±3.4) of DS compared to naïve mice (9.9±1.3).
These data demonstrate that stress-induced damage to the ocular surface resembling Dry Eye can occur independently of chronic T cell-mediated disease.
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