Ocular Surface Involvements in the Development of Sjögren's Syndrome–Associated Dry Eye in the IL14α Transgenic Mouse

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Purpose: To investigate the ocular surface changes during progress of the Sjögren's Syndrome (SS), using a previously described IL14α transgenic mice (IL14α TG) SS model. Methods: The ocular surface of IL14α TG and C57BL/6 wild-type (WT) female mice were evaluated at the age of six, nine, 12, 15, and 18 months. Slit lamp microscopy observation, Oregon green dextran staining, Schirmer test, and periodic-acid-Schiff staining were assessed. Immunohistochemistry, immunofluorescence, and associated gene expression analysis by qPCR and ELISA were performed in cornea, conjunctiva, and lacrimal grand at different ages of the mice. Masson's trichome staining was conducted on lacrimal gland cryosections. Results: Compared with C57BL/6 WT mice, IL14α TG mice showed corneal barrier function damage and losses in conjunctival goblet cell density starting at nine months, whereas decreases in tear secretion started at 18 months of age. Significant increases in CD4+ T cell infiltration in the conjunctiva of IL14α TG mice was first observed at 6 months. Higher expression levels of inflammatory cytokines IL-17A, IFN-γ, IL-1β, and TNF-α in the conjunctiva, whereas MUC5AC and MUC5B had lower expression levels at nine months in the IL14α TG mice. However, lacrimal gland function-associated gene expression levels mostly decreased in IL14α TG mice at 12 months of age. Conclusions: Ocular surface tissue changes were involved in SS-like dry eye in a time-dependent manner in IL14α TG mice, and conjunctival T-cell infiltration may contribute to ocular surface pathological changes in an early stage of SS-related dry eye.

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