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William Foulsham, Yihe Chen, Takeshi Nakao, Man Yu, Sunil Chauhan, Reza Dana; Severe dry eye disease in aged mice is associated with an expanded memory Th17 cell response and higher frequencies of IFN-γ-expressing Th17 Cells. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3286.
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The prevalence and severity of dry eye disease increases with age, but the immunopathological mechanisms that contribute towards this phenomenon have not been defined. Using a well-characterized murine model of dry eye disease, we evaluated the susceptibility of aged mice to develop ocular surface epitheliopathy in response to desiccating stress, and characterized the effector immune response.
Dry eye disease was induced in female C57BL/6 mice aged 6-8 weeks or 12-14 months using a controlled environmental chamber for 14 days. Mice were subsequently housed in a standard vivarium for 21 days, before re-exposure to desiccating stress. Corneal fluorescein staining was used to assess dry eye disease severity. Frequencies of memory Th17 (IL-17A+CD44+), Th1, Th17, and Th17/1 (IL-17+IFN-γ+) cells were assessed in draining lymph nodes by flow cytometry at day 35 (prior to rechallenge) and day 59 (after rechallenge).
Aged mice exhibited a greater increase in corneal fluorescein staining scores following re-exposure to desiccating stress, relative to young mice (P<0.001). Flow cytometry data demonstrated a larger population of memory Th17 cells in aged mice relative to young mice prior to rechallenge (P<0.001). Following rechallenge, aged mice demonstrated higher frequencies of ‘double-positive’ Th17/1 lymphocytes compared to young mice (P=0.009).
Re-exposure to desiccating stress results in a greater increase in corneal epitheliopathy in aged mice relative to young. Our data show aged mice have significantly higher frequencies of memory Th17 cells prior to rechallenge, and greater frequencies of double-positive Th17/1 lymphocytes after rechallenge.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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