Interferon-gamma deficiency protects against aging-related goblet cell loss.
Aging is a well-recognized risk factor for dry eye. Interferon-gamma (IFN-γ) has been implicated in conjunctival keratinization and goblet cell loss in dry eye. We investigated the role of IFN-γ in age-related dry eye by evaluating young (8 weeks) and aged (15 months; 15M) C57BL/6 (B6) and IFN-γKO mice. Age effects on the conjunctiva and cornea epithelium were assessed with PAS staining and corneal staining, respectively. Expression of T cell-related cytokines (IL-17A, IFN-γ), chemokines (CXCL10 and CCL20), in the ocular surface epithelium was evaluated by real time PCR. A significant decrease in filled goblet cells was noted in 15M B6 mice and this was significantly lower than age and sex-matched IFN-γKO mice. Aged male B6 had significantly higher IFN-γ, and CXCL10 mRNA in their conjunctiva than female B6 mice. Aged IFN-γKO females had significantly higher IL-17A mRNA in conjunctiva than IFN-γKO males and B6 mice. Corneal barrier dysfunction was observed in 15M female B6 and aged IFN-γKO mice of both sexes; however it was significantly higher in IFN-γKO compared to B6 mice. While there was a significant increase in IL 17A, and CCL20 in corneas of aged female B6 and IFN-γKO mice compared to males, these changes were more evident in aged female IFN-γKO group.Partial resistance of IFN-γKO mice to aging-induced goblet cell loss indicates IFN-γ is involved in the age-related decline in conjunctival goblet cells. Increased corneal IL-17A expression paralleled corneal barrier disruption in aging female of both strains. IFN-γ appears to suppress IL-17A on the ocular surface.
Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, Texas, USA.
Eugene A
EA
Volpe
Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, Texas, USA.
Johanna Tukler
JT
Henriksson
Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, Texas, USA.|Eye Center, Second Affiliated Hospital of Zhejiang University, School of Medicine Zhejiang Provincial Key Laboratory of Ophthalmology, Hangzhou, Zhejiang, China.
Changjun
C
Wang
Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, Texas, USA.
Flavia L
FL
Barbosa
Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, Texas, USA.
Mahira
M
Zaheer
Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, Texas, USA.|Eye Institute of Xiamen University, Xiamen, Fujian, China.
Xiaobo
X
Zhang
Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, Texas, USA.
Stephen C
SC
Pflugfelder
Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, Texas, USA.
Cintia S
CS
de Paiva
D000375:Aging / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D054418:Chemokine CCL20 / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000378:metabolism; D003228:Conjunctiva / Q000473:pathology*; D003315:Cornea / Q000473:pathology*; D004195:Disease Models, Animal; D015352:Dry Eye Syndromes / Q000276:immunology*; D005260:Female; D020397:Goblet Cells / Q000502:physiology*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology*
C493447:CCL20 protein, mouse; D054418:Chemokine CCL20; D054357:Chemokine CXCL10; C485433:Cxcl10 protein, mouse; D020381:Interleukin-17; D007371:Interferon-gamma
Gerotarget; IL-17; aging; dry eye; goblet cells; interferon-gamma