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Justin A Courson, Carolina Lema, Betty Zhang, Rachel L Redfern; The role of IL-1R and MyD88 in a murine model of experimental dry eye. Invest. Ophthalmol. Vis. Sci. 2016;57(12):405.
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© ARVO (1962-2015); The Authors (2016-present)
Previously we have shown that experimental dry eye (EDE) increases toll-like receptor (TLR) expression on the mouse cornea and conjunctiva, which we hypothesize is a source of inflammatory cytokines and matrix metalloproteinases (MMP). This study examines changes in ocular surface inflammation in C57BL/6 (WT), interleukin (IL)-1R-/- and MyD88-/- (deficient in TLR and IL-1R function) mice following EDE.
EDE was induced in 6-8 week old C57BL/6 (WT), MyD88-/-, and IL-1R-/- male and female mice by subcutaneous scopolamine injection (TID) and desiccating stress for 5 days. Following treatment, tear production (phenol red thread test) and corneal fluorescein staining were assessed. Tear, conjunctiva and corneal epithelial protein samples were analyzed using mouse cytokine/chemokine multiplex magnetic bead panel assay.
Following EDE treatment, WT and IL-1R-/- mice showed a significant increase in ocular surface staining, while no significant difference was found in MyD88-/- mice compared to untreated littermates. Tear production was significantly reduced in all genotypes following EDE, although both IL-1R-/- and MyD88-/- mice exhibited lower levels of baseline tear production. EDE significantly (P≤0.05) increased the levels of cytokine-induced neutrophil chemoattractant (KC) in WT corneal epithelium, which was reduced or abolished in the IL-1R-/- or MyD88-/- EDE mice respectively. After treatment, conjunctival IL-2 and IL-9 levels were decreased in WT, not changed or decreased in IL-1R-/- mice and significantly increased (P≤0.001) in MyD88-/- mice. Baseline KC, IL-2 and IL-9 were significantly (P≤0.05) reduced compared to WT and EDE in the cornea. RANTES was increased in tear samples following treatment but remained low in both IL-1R-/- and MyD88-/- mice compared to WT EDE mice.
The loss of functional TLRs results in reduced ocular surface damage, reduced inflammatory cytokines, and an increase in Th2 cytokines. This data suggests that TLRs play a role in modulating the inflammation and damage associated with dry eye disease.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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