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A. J. McClellan, W. J. Farley, S. C. Pflugfelder, C. S. De Paiva; Spontaneous Dry Eye Phenotype is Associated With Autoimmunity in Older Mice. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3393.
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Dry eye is a more prevalent disease in the elderly. The purpose of this study was to characterize the ocular surface and lacrimal gland changes that occur with natural aging.
Three age groups were evaluated: 8 week-old (8W), retired breeder (6-9 months-old, RB), and 24 month-old (24M) C57BL/6 mice. Eyes, adnexae, and extraorbital lacrimal glands were excised and prepared for either histology or frozen sections. Goblet cells (GC) were identified for counting with PAS staining. Corneal smoothness was assessed by reflection of a ring off the corneal surface. Immunohistochemistry was used to identify and count cells that were positive(+) for CD4, CD8, CD11b, CD11c, or IAIE in corneal and conjunctival tissue. The phenotype of antigen-presenting cells (APC) was assessed by dual immunofluorescent staining for CD11b or CD11c and IAIE in corneal sections.
24M mice spontaneously exhibit a dry eye phenotype compared to younger 8W mice, characterized by increased corneal irregularity, decreased conjunctival GC, and an increased number of CD4+, CD8+ , CD11b+, CD11c+, and IAIE+ cells in the conjunctival epithelium (p<0.05 for all). RB mice have a significant increase in corneal irregularity, decreased GC density,a decrease in the number of CD8+ cells and an increase in CD11b+ and IAIE+ cells in the conjuntival epithelium (p<0.05 for all). 24M mice also show a significant increase in IAIE+, CD11b+, and CD11c+ cells in the peripheral cornea (p<0.05 for all). While no change in CD11b+ cells was seen, a significant increase in IAIE and CD11c+ cells was noted for both RB and 24M groups in the central cornea (p <0.05 for both), compared to 8W mice. The majority of these CD11c+ cells also expressed IAIE.
Aging in mice was associated with increased corneal surface irregularity and decreased conjuntival GC density which is chartacteristic of dry eye. These changes were accompanied by immunopathological changes in the cornea and conjunctiva. These findings suggest that aging is associated with immune disregulation and autoimmunity that may promote the development of dry eye.
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