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P.L. Christopherson, J. Smith, G. Sosne; Early Corneal and Lacrimal Gland Expression of Inflammatory Genes in a Murine model of Sjogren's Syndrome . Invest. Ophthalmol. Vis. Sci. 2005;46(13):4462.
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Purpose: The purpose of this study was to investigate early inflammatory gene expression differences in corneas and lacrimal glands from normal [C57BL/6J (BL/6)] and Sjogren’s Syndrome–like B6.MRL Tnfrsf6lpr (MRL/lpr) mice. Methods:8 week old BL/6 and MRL/lpr (n=8/group) mice were sacrificed and the eyes and lacrimal glands were grossly examined and analyzed histologically (H & E staining). Corneas and lacrimal glands were also prepared for RNA and protein analyses. Results: Gross examination and histological analysis showed no apparent inflammatory differences between the groups. However, RT–PCR analysis revealed significant induction of several inflammatory gene mRNA levels in the corneas and lacrimal glands from the MRL/lpr mice compared to BL/6. MRL/lpr corneas had a 1.5 to 8 fold increase over BL/6 for Caspases 1, 3 and 9, for interleukin (IL)–1ß, KC, macrophage inflammatory protein (MIP) –2, matrix metalloproteinase (MMP)–9, plasminogen activator inhibitor (PAI) –1, transforming growth factor (TGF)–ß1, tumor necrosis factor (TNF)–α, and Toll–like receptors (TLR) –4 and –5. Lacrimal gland changes were not as dramatic but showed MRL/lpr increased expression levels over BL/6 for Caspase 1, IL1ß, IL–18, KC, MMP–9, TGFß1 and TLR–4. Conclusions: The MRL/lpr mouse model for inflammatory dry eye disease is useful in determining molecular changes in early corneal and lacrimal gland inflammation in the absence of histolopathological correlation. These novel results suggest that anti–inflammatory therapies initiated before tissue destruction occurs may ameliorate the deleterious dry eye and ocular surface manifestations of Sjogren’s Syndrome.
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