Purchase this article with an account.
Justin Courson, Carolina Lema, Rachel L Redfern; The Role of Toll-like Receptors in Experimental Dry Eye Inflammation. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3049.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
We hypothesize that toll-like receptors (TLRs) play a role in dry eye inflammation. We have previously shown that hyperosmolar stress modulates TLR expression and the release of endogenous damage associated molecular patterns (DAMPs) which may activate TLRs to produce cytokines and matrix metalloproteinases (MMPs). In support of this, we have shown that topical TLR agonists induce corneal ulceration in mice undergoing experimental dry eye. In this current study, we use MyD88 knock out (loss of functioning TLRs) mice to investigate the role of TLRs in dry eye pathology.
Experimental dry eye (EDE) was induced in six to eight week old wild-type and MyD88 knock out (KO) C57BL/6 mice by scopolamine hydrobromide injections and environmental stress (10-20% humidity and constant air draft). Untreated mice were kept in a controlled environment under standard housing conditions (50-60% relative humidity). After five days of treatment, tear production and ocular surface damage were accessed using phenol red thread test (PRT) and corneal fluorescein staining respectively. Following this, the eyes and lids were removed and processed for frozen tissue sectioning. Goblet cell counts were obtained after periodic acid schiff staining and the level of MMP9 on the ocular surface was determined by immunohistochemistry.
Both wild-type and MyD88 KO animals who underwent experimental dry eye showed significant increases in ocular surface staining (p<0.02), and a significant reduction in tear production via PRT test when compared to untreated wild-type controls (p<0.01). In addition, experimental dry eye MyD88 KO mice experienced a significant decrease in ocular surface staining when compared to wild-type mice under experimental dry eye (p<0.03). Goblet cell counts were significantly increased in MyD88 animals who underwent experimental dry eye when compared to their wild-type counterparts (p<0.01).
This preliminary data suggests that TLRs play a role in modulating ocular surface damage resulting from dry eye. It is also known that TLRs play a protective role in pathogen recognition enabling an innate immune response to microbes. When attempting to alleviate dry eye symptoms it is important to maintain an ability to fight pathogens, as such determining the exact role of TLRs in dry eye inflammation is imperative for developing novel treatments that modulate inflammation without increasing the risk for infection.
This PDF is available to Subscribers Only