title: Age-Related Conjunctival Disease in the C57BL/6.NOD-Aec1Aec2 Mouse Model of Sjögren Syndrome Develops Independent of Lacrimal Dysfunction.
abstract: OBJECTIVE
  To investigate parameters of ocular surface disease in C57BL/6.NOD-Aec1Aec2 (Aec) mice with aging and their correlation with development of Sjögren syndrome (SS)-like lacrimal gland (LG) disease.
  
  
  METHODS
  Aec and C57BL/6 wild-type (B6) female mice were evaluated at 4, 12, and 20 weeks of age. Whole LG and eyes and adnexa were excised for histology and gene expression analysis and evaluated by flow cytometry and immunohistochemistry. Tear volume and goblet cell density was measured. Quantitative PCR evaluated T-cell-related cytokine expression in cornea and conjunctiva.
  
  
  RESULTS
  Both strains showed age-related conjunctival goblet cell loss that was more pronounced in the Aec strain and significantly greater than in B6 mice at 12 weeks. This was accompanied by CD4+ T-cell infiltration of the conjunctiva that was greater in Aec strain at 20 weeks. Aec mice had higher levels of IL-17A, IL-17R, IL-1α, IL-1β, and TNF-α in the conjunctiva, and they significantly increase with aging. Aec mice had greater lymphocytic infiltration of the LG and conjunctiva at 20 weeks that consisted of a mixture of CD4+ and CD8+ cells. Flow cytometry showed a significant increase in CD4+ T cells in Aec LG compared to B6 mice. Tear volume was significantly increased in both strains at 20 weeks.
  
  
  CONCLUSIONS
  Aec mice developed greater conjunctival goblet cell loss associated with lymphocytic infiltration of the LG and conjunctiva with aging. Increased expression of certain T helper or inflammatory cytokines in these tissues was observed in Aec mice. The conjunctival disease appeared to be due to inflammation and not a decrease in tear volume.
authors.affiliation: Department of Ophthalmology, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Jeonbuk, Korea 2Ocular Surface Center, Department of Ophthalmology, Cullen Eye.
authors.forename: In-Cheon
authors.initials: IC
authors.lastname: You
authors.affiliation: Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, Texas, United States.
authors.forename: Fang
authors.initials: F
authors.lastname: Bian
authors.affiliation: Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, Texas, United States.
authors.forename: Eugene A
authors.initials: EA
authors.lastname: Volpe
authors.affiliation: Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, Texas, United States.
authors.forename: Cintia S
authors.initials: CS
authors.lastname: de Paiva
authors.affiliation: Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, Texas, United States.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Pflugfelder
mesh_terms: D000367:Age Factors; D000818:Animals; D003229:Conjunctival Diseases / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007765:Lacrimal Apparatus / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D012859:Sjogren's Syndrome / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D013666:Tears / Q000378:metabolism*
chemical_list: D016207:Cytokines