MyD88 Deficiency Protects Against Dry Eye-Induced Damage

Invest Ophthalmol Vis Sci. 2018 Jun 1;59(7):2967-2976. doi: 10.1167/iovs.17-23397.


Purpose: Dry eye disease (DED) is a multifactorial disease associated with ocular surface inflammation. Toll-like receptors (TLRs) are integral in the initiation of inflammatory signaling. Therefore, we evaluated the effect of TLR-deficiency on dry eye-related ocular surface damage and inflammation using a mouse model of experimental dry eye (EDE).

Methods: C57BL/6 wild-type (WT), MyD88-/-, and IL-1R-/- mice were exposed to EDE conditions for 5 days. Tear production was measured by phenol red thread test and ocular surface damage assessed with fluorescein staining. Corneal homogenates were obtained for matrix metalloproteinase (MMP) and cytokine expression analysis by Luminex assay and quantitative PCR. In addition, whole eyes and eyelids were dissected and goblet cells and Meibomian glands were imaged, respectively.

Results: Following 5 days of EDE, WT mice had extensive ocular surface staining, while MyD88-/- mice had no increased staining above non-EDE conditions. Similarly, MyD88-/- mice did not have increased corneal MMP-2, 3, or 8 concentrations, as seen with WT mice. MyD88-deficiency also resulted in decreased corneal cytokine levels. In addition, MyD88-/- mice had significantly lower conjunctival goblet cell counts compared with both WT (EDE) and IL-1R-/- (non-EDE) mice. However, there was no difference in Meibomian gland morphology between WT, IL-1R-/-, and MyD88-/- mice.

Conclusions: These studies demonstrate the importance of TLR signaling in dry eye development. Mice lacking TLR signaling, MyD88-/-, were protected from EDE-induced ocular surface damage and inflammatory mediator expression, warranting further investigation into TLR inhibition as a potential therapeutic for DED.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Count
  • Cytokines / genetics
  • Cytokines / metabolism
  • Disease Models, Animal*
  • Dry Eye Syndromes / metabolism
  • Dry Eye Syndromes / pathology
  • Dry Eye Syndromes / prevention & control*
  • Fluorescent Antibody Technique, Indirect
  • Goblet Cells / pathology
  • Immunologic Deficiency Syndromes / complications*
  • Matrix Metalloproteinases / genetics
  • Matrix Metalloproteinases / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Myeloid Differentiation Factor 88 / deficiency*
  • Primary Immunodeficiency Diseases
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction / physiology
  • Tears / metabolism
  • Tomography, Optical Coherence


  • Cytokines
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Matrix Metalloproteinases

Supplementary concepts

  • MYD88 Deficiency