IFN– Promotes Goblet Cell Loss in Response to Desiccating Ocular Stress

Abstract

Purpose: : To investigate the effects of desiccating stress on number and location of conjunctival T cells and the effects of Th–1 and Th–2 cytokines on conjunctival goblet cell loss.

Methods: : C57BL6 and BALB/c mice aged 6–8 weeks were treated with systemic scopolamine and exposure to an air draft for 5 or 12 days (D) to induce experimental dry eye (EDE). Immunohistochemistry was used to evaluate the number and location of infiltrating cells expressing T cell markers (CD4 and CD8) and the cytokines interferon–gamma (IFN–γ) and interleukin (IL)–4 in the conjunctiva. C57BL6, BALB/c and IFN–γ knock–out (B6γKO) were subjected to EDE and received subconjunctival injections of IFN–γ. Goblet cell density was evaluated by PAS staining.

Results: : Marked differences in cellular profiles of T cell infiltrates in the conjunctiva were observed between the two strains exposed to desiccating stress. EDE caused a significant increase in the number of CD4+ cells (5D and 12D) and IFN–γ+ cells (a Th–1 cytokine, 12D) and a concomitant decrease in CD8+ cells (5D and 12D) in the conjunctival epithelium of C57BL6 mice, which are Th–1 prone. The CD4/CD8 ratio was greater in C57BL6 than BALB/c (which are Th–2 prone) after 5D and 12D of EDE. No staining for IL–4, a Th–2 cytokine, was noted in either mouse strain. C57BL6 mice had significantly greater goblet cell loss than BALB/c mice and the greatest goblet cell loss was noted in areas of CD4+ T cell infiltration. Subconjunctival administration of IFN–γ induced significant goblet cell loss in C57BL6 mice after 5D of EDE. In B6γKO mice, desiccating stress had no effect on the number of goblet cells, howerver exogenous administration of IFN–γ markedly decreased the goblet cell density.

Conclusions: : Desiccating stress promotes CD4+ T cell infiltration and increases the CD4/CD8 ratio of T cells that infiltrate in the conjunctival epithelium of C57BL6 mice. The Th–1 cytokine IFN–γ appears to affect the disappearance of goblet cells in areas of CD4+ T cell infiltration.

Keywords: cornea: tears/tear film/dry eye • cytokines/chemokines • inflammation