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In-Chon Yu, Eugene Volpe, Fang Bian, Stephen C Pflugfelder, Cintia S. De Paiva; Ocular Surface and Lacrimal Gland Alterations in the C57BL/6.NOD-Aec1Aec2 Mouse Model of Sjögren’s Syndrome. Invest. Ophthalmol. Vis. Sci. 2014;55(13):61.
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© ARVO (1962-2015); The Authors (2016-present)
C57BL/6.NOD-Aec1Aec2 (AEC) mouse develops spontaneously Sjögren’s syndrome (SS)-like disease with aging, but there is scarce information about the ocular surface. Hereby we investigated parameters of ocular surface disease in AEC mice with aging and their correlation with development of LG disease.
C57BL/6.NOD-Aec1Aec2 female mice were evaluated at 4, 12, and 20 weeks (W) of age and C57BL/6 wild type (WT) female mice were used as controls. Tear volume was measured using the cotton thread test. Whole lacrimal gland and eyes and adnexa were excised for histology or used for gene expression analysis. Lacrimal gland (LG) infiltrating lymphocytes were characterized with flow cytometry. Phenotype of lymphocytes infiltrating the LG and conjunctiva was evaluated by immunohistochemistry. Goblet cell density was measured in PAS stained sections. Quantitative polymerase chain reaction evaluated T-cell-related cytokine expression in conjunctiva.
Both strains showed similar increase in tear volume with aging from 4 to 20 weeks of age. AEC mice had increased lymphocytic infiltration of the LG and conjunctiva at 20 weeks, consisting of mixture of CD4 and CD8+ cells. Flow cytometry showed a significant increase in CD4+ in AEC LG compared to WT at 12 and 20W (16.08 ± 4.0 and 17.08 ± 3.2 vs. 6.57 ± 1.5 and 8.73 ± 2.7 %, P<0.01 for both). AEC mice had significantly higher levels of IFN-γ, IL-1β, and IL-6 mRNA transcripts in the LG than WT mice at 4 and 12 weeks (P<0.01 for all). We noted a significant increase in CD4+ T cell infiltration in conjunctival epithelium in AEC mice compared to WT at 20 weeks (2.07 ± 0.32 vs. 1.46 ± 0.41 cells, p=0.01), while goblet cell density was significantly lower in AEC mice at 12 and 20W. AEC mice had higher levels of IL-17A and IL-1α (at 4, 12, 20W), TNF-α, IL-1β (at 12 and 20W) and significantly lower levels of MHC II mRNA transcripts (at 4, 12, 20W) in the conjunctiva compared the WT mice. There was a significant age-related increase in expression of IL-17, IL-1α, IL-1β and TNF-α in AEC conjunctiva with aging from 4 to 20W.
Although both LG and ocular surface of C57BL/6.NOD-Aec1Aec2 mice developed infiltration with aging with accompanying inflammation, the findings in ocular surface were not related to decreased tear volume.
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