Ocular Surface Disease and Dacryoadenitis in Aging C57BL/6 Mice

• Published in: The American journal of pathology Vol. 184; no. 3; pp. 631 - 643
• Main Authors: McClellan, Andrew J, Volpe, Eugene A, Zhang, Xiaobo, Darlington, Gretchen J, Li, De-Quan, Pflugfelder, Stephen C, de Paiva, Cintia S
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2014; American Society for Investigative Pathology
• Subjects: Adoptive Transfer; Aging - pathology; Animals; Autoimmunity; CD8-Positive T-Lymphocytes - metabolism; Cornea - pathology; Dacryocystitis - metabolism; Dacryocystitis - pathology; Disease Models, Animal; Dry Eye Syndromes - metabolism; Dry Eye Syndromes - pathology; Eye - pathology; Female; Goblet Cells - metabolism; Humans; Interleukin-17 - genetics; Interleukin-17 - metabolism; Lacrimal Apparatus - cytology; Lacrimal Apparatus - immunology; Lacrimal Apparatus - metabolism; Male; Mice; Mice, Inbred C57BL; Pathology; Phenotype; Regular; Severity of Illness Index; Th1 Cells - metabolism; Th17 Cells - metabolism
• ISSN: 0002-9440; 1525-2191
• DOI: 10.1016/j.ajpath.2013.11.019

Dry eye in humans displays increased prevalence in the aged and in women. Here, we investigated the ocular surfaces and lacrimal glands of aged mice of both sexes. We surveyed three different ages [young, middle-aged (6 to 9 months), and elderly] by investigating severity markers of dry eye disease (DED). We observed an age-dependent dry eye phenotype as early as 6 to 9 months: increased corneal surface irregularity, increased corneal barrier disruption, conjunctival CD4+ T-cell infiltration, and loss of mucin-filled goblet cells. Expression of interferon-γ, IL-17 mRNA transcripts was increased in the conjunctiva and IL-17A, matrix metallopeptidase 9, and chemokine ligand 20 in the corneas of elderly mice. Elderly male mice develop more of a skewed response of type 1 T helper cell, whereas female mice have a bias toward type 17 T helper cell in the conjunctiva. In the lacrimal gland, an increase in CD4+ and CD8+ T cells and B cells and a decrease in activated dendritic cells were observed. Adoptive transfer of CD4+ T cells isolated from elderly mice transferred DED into young immunodeficient recipients, which was more pronounced from male donors. Our findings show the development of DED in aging mice. Pathogenic CD4+ T cells that develop with aging are capable of transferring DED from older mice to naive immunodeficient recipients. Taken together, our results indicate that age-related autoimmunity contributes to development of DED with aging.