In-Cheon You1, Fang Bian2, Eugene A Volpe2, Cintia S de Paiva2, Stephen C Pflugfelder2. 1. 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. 2. Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, Texas, United States.
Abstract
PURPOSE: 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.
PURPOSE: 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: Ehsan Rahimy; John D Pitcher; Solherny B Pangelinan; Wei Chen; William J Farley; Jerry Y Niederkorn; Michael E Stern; De-Quan Li; Stephen C Pflugfelder; Cintia S De Paiva Journal: Am J Pathol Date: 2010-06-21 Impact factor: 4.307
Authors: Gikas E Katsifis; Sofia Rekka; Niki M Moutsopoulos; Stanley Pillemer; Sharon M Wahl Journal: Am J Pathol Date: 2009-08-21 Impact factor: 4.307
Authors: Cintia S De Paiva; Cindy S Hwang; John D Pitcher; Solherny B Pangelinan; Ehsan Rahimy; Wei Chen; Kyung-Chul Yoon; William J Farley; Jerry Y Niederkorn; Michael E Stern; De-Quan Li; Stephen C Pflugfelder Journal: Rheumatology (Oxford) Date: 2009-12-09 Impact factor: 7.580
Authors: C S De Paiva; S Chotikavanich; S B Pangelinan; J D Pitcher; B Fang; X Zheng; P Ma; W J Farley; K F Siemasko; J Y Niederkorn; M E Stern; D-Q Li; S C Pflugfelder Journal: Mucosal Immunol Date: 2009-02-25 Impact factor: 7.313
Authors: Mark D P Willcox; Pablo Argüeso; Georgi A Georgiev; Juha M Holopainen; Gordon W Laurie; Tom J Millar; Eric B Papas; Jannick P Rolland; Tannin A Schmidt; Ulrike Stahl; Tatiana Suarez; Lakshman N Subbaraman; Omür Ö Uçakhan; Lyndon Jones Journal: Ocul Surf Date: 2017-07-20 Impact factor: 5.033
Authors: Changjun Wang; Mahira Zaheer; Fang Bian; Darin Quach; Alton G Swennes; Robert A Britton; Stephen C Pflugfelder; Cintia S de Paiva Journal: Int J Mol Sci Date: 2018-02-13 Impact factor: 5.923