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S. Li, K. Nikulina, T. Vijmasi, N. McNamara; Development of Ocular Surface Disease in aire-Deficient Mice. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5332.
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Balb/c mice deficient in the autoimmune regulator (aire) gene provide a model of autoimmune-mediated aqueous-deficient dry eye disease that resembles human Sjögren’s Syndrome (SS). In a previous study, we showed a definitive link between inflammation and ocular surface disease. Here we examine the kinetics of the dry eye phenotype by monitoring the development of ocular surface disease and the expression of inflammatory cytokines in aire-deficient mice at 4, 8 and 16 weeks.
Punctate epithelial erosion of the cornea was assessed in aire-knockout mice and aire-heterozygous controls with lissamine green. CD4+ and CD8+ T cells were monitored in the cornea, conjunctiva and lids by immunohistochemistry. Goblet cells were quantified by PAS staining. The expression of cytokines and squamous metaplasia marker, small proline-rich protein 1B (SPRR1B) was assessed by immunohistochemistry and quantitative real-time PCR.
Punctate epithelial erosion of the cornea developed in aire-knockout mice as early as 4 weeks and progressed to filamentary keratitis over time. CD4+ T cells infiltrated the cornea and lid tissues by 4 weeks. The number of goblet cells decreased over time while the mRNA levels of SPRR1B, IFN-γ and IL-1β increased in aire-knockout mice compared to heterozygous littermates.
The mouse model of aire-deficiency mimics the ocular surface disease observed in human patients with autoimmune-mediated aqueous-deficient dry eye. Signs of ocular surface damage begin as early as 4 weeks and progress in severity over time. As the disease progresses, squamous metaplasia occurs and the expression of inflammatory cytokines increases. These changes are also observed in human patients with SS.
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