Oncotarget

Research Papers: Gerotarget (Focus on Aging):

Interferon-gamma deficiency protects against aging-related goblet cell loss

Eugene A. Volpe, Johanna Tukler Henriksson, Changjun Wang, Flavia L. Barbosa, Mahira Zaheer, Xiaobo Zhang, Stephen C. Pflugfelder and Cintia S. de Paiva _

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Oncotarget. 2016; 7:64605-64614. https://doi.org/10.18632/oncotarget.11872

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Abstract

Eugene A. Volpe1, Johanna Tukler Henriksson1, Changjun Wang1,2, Flavia L. Barbosa1, Mahira Zaheer1, Xiaobo Zhang1,3, Stephen C. Pflugfelder1 and Cintia S. de Paiva1

1 Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, Texas, USA

2 Eye Center, Second Affiliated Hospital of Zhejiang University, School of Medicine Zhejiang Provincial Key Laboratory of Ophthalmology, Hangzhou, Zhejiang, China

3 Eye Institute of Xiamen University, Xiamen, Fujian, China

Correspondence to:

Cintia S. de Paiva, email:

Keywords: aging; dry eye; interferon-gamma; goblet cells; IL-17; Gerotarget

Received: May 10, 2016 Accepted: September 01, 2016 Published: September 06, 2016

Abstract

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.


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