The conjunctiva is a goblet cell rich mucosal tissue. Goblet cells are supported by tear growth factors and IL-13 produced by resident immune cells. Goblet cell secretions are essential for maintaining tear stability and ocular surface homeostasis. In addition to producing tear stabilizing mucins, they also produce cytokines and retinoic acid that condition monocyte-derived phagocytic cells in the conjunctiva. Aqueous tear deficiency from lacrimal gland disease and systemic inflammatory conditions results in goblet cell loss that amplifies dry eye severity. Reduced goblet cell density is correlated with more severe conjunctival disease, increased IFN-γ expression and antigen presenting cell maturation. Sterile Alpha Motif (SAM) pointed domain epithelial specific transcription factor (Spdef) gene deficient mice that lack goblet cells have increased infiltration of monocytes and dendritic cells with greater IL-12 expression in the conjunctiva. Similar findings were observed in the conjunctiva of aged mice. Reduced retinoic acid receptor (RXRα) signaling also increases conjunctival monocyte infiltration, IFN-γ expression and goblet cell loss. Evidence suggests that dry eye therapies that suppress IFN-γ expression preserve conjunctival goblet cell number and function and should be considered in aqueous deficiency.
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