title: Ocular surface disease and dacryoadenitis in aging C57BL/6 mice.
abstract: 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.
authors.affiliation: Department of Ophthalmology, Ocular Surface Center, Cullen Eye Institute, Houston, Texas.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McClellan
authors.affiliation: Department of Ophthalmology, Ocular Surface Center, Cullen Eye Institute, Houston, Texas.
authors.forename: Eugene A
authors.initials: EA
authors.lastname: Volpe
authors.affiliation: Department of Ophthalmology, Ocular Surface Center, Cullen Eye Institute, Houston, Texas; Shenyang He Eye Hospital, Shenyang, Liaoning Province, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Huffington Center on Aging, Baylor College of Medicine, Houston, Texas.
authors.forename: Gretchen J
authors.initials: GJ
authors.lastname: Darlington
authors.affiliation: Department of Ophthalmology, Ocular Surface Center, Cullen Eye Institute, Houston, Texas.
authors.forename: De-Quan
authors.initials: DQ
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, Ocular Surface Center, Cullen Eye Institute, Houston, Texas.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Pflugfelder
authors.affiliation: Department of Ophthalmology, Ocular Surface Center, Cullen Eye Institute, Houston, Texas. Electronic address: cintiadp@bcm.edu.
authors.forename: Cintia S
authors.initials: CS
authors.lastname: de Paiva
mesh_terms: D019264:Adoptive Transfer; D000375:Aging / Q000473:pathology; D000818:Animals; D015551:Autoimmunity; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D003315:Cornea / Q000473:pathology; D003607:Dacryocystitis / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D015352:Dry Eye Syndromes / Q000378:metabolism / Q000473:pathology*; D005123:Eye / Q000473:pathology; D005260:Female; D020397:Goblet Cells / Q000378:metabolism; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism; D007765:Lacrimal Apparatus / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D012720:Severity of Illness Index; D018417:Th1 Cells / Q000378:metabolism; D058504:Th17 Cells / Q000378:metabolism
chemical_list: D020381:Interleukin-17