Abstract
Purpose :
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.
Methods :
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.
Results :
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.
Conclusions :
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.