Aqueous Tear Deficiency Increases Conjunctival Interferon-γ (IFN-γ) Expression and Goblet Cell Loss

Abstract

Interferon-γ expression in the conjunctiva was higher in aqueous deficiency and correlated with goblet cell loss and severity of conjunctival disease. These results support findings of animal and culture studies showing that IFN-γ reduces conjunctival goblet cell number and mucin production.

Goblet cell loss abrogates ocular surface immune tolerance

“…Epithelial cells in the intestine and stomach have also been noted to produce RA that functions to maintain immune tolerance in these tissues (21,22). Our findings suggest that the conjunctival GCs have homeostatic immunomodulatory activity that promotes generation of Tregs, while suppressing generation of IFN-γ-producing T cells that can amplify dry eye disease by promoting GC loss and secretory dysfunction (3,23).…”

“…Loss of tolerance in the dry eye group was confirmed by increased DTH to OVA antigen, reduced T cell suppression of antigen-specific T cell proliferation, and increased generation of IFN-γ-and IL-17-positive CD4 + T cells (10). Both of these T helper cytokines have been implicated in the pathogenesis of the ocular surface epithelial disease that develops in dry eye (6,23,25).…”

“…There is a loss of mucus-producing conjunctival goblet cells (GCs) in aqueous-deficient dry eye due to increased IFN-γ expression that causes GC secretory dysfunction and death (1)(2)(3). Dry eye is increasingly recognized as an immune-based inflammatory condition.…”

Tear Interferon-Gamma as a Biomarker for Evaporative Dry Eye Disease

“…11,13 Higher conjunctival expression of IFN-c has recently been reported in individuals with non-Sjögren and Sjögren syndrome-associated aqueousdeficient DED. 41 Moreover, increased IFN-c expression was shown to correlate with the degree of goblet cell loss, extent of reduced mucin production, and the severity of conjunctival pathology. 41 It is therefore noteworthy that we find elevated tear osmolarity to be specifically associated with increased tear concentrations of IFN-c and that this finding has a large Cohen's effect size, indicating the importance of the finding independent of sample size.…”

“…41 Moreover, increased IFN-c expression was shown to correlate with the degree of goblet cell loss, extent of reduced mucin production, and the severity of conjunctival pathology. 41 It is therefore noteworthy that we find elevated tear osmolarity to be specifically associated with increased tear concentrations of IFN-c and that this finding has a large Cohen's effect size, indicating the importance of the finding independent of sample size. In addition, there was a significant positive correlation between increasing tear osmolarity and higher tear IFN-c levels (r ¼ 0.34; P ¼ 0.007).…”