Abstract
Purpose :
Dry eye disease (DED) is the most common ocular surface disease, average one out of every five persons suffered by this disease in the worldwide. Accumulating evidence demonstrates that immunoinflammatory mechanisms play pivotal roles in the pathogenesis of DED. However, the potential roles and mechanism of innate immune are largely unknown.
Methods :
In the present study, we used an experimental murine dry eye model and in vitro human limbal epithelial cell (HLEC) dry eye model induced by hyperosmotic stress to investigate the underlying mechanisms of innate immune in DED.
Results :
We found that caspase-8 activated by ROS play a key role in the pathogenesis of DED by forming a caspase-8-ASC inflammasome, promoting the activation of NLRP3 inflammasome and downregulating NLRP6 inflammasome via NF-κB pathway. The activation of NLRP3 inflammasome can also suppress the production of NLRP6 and promote the processing of IL-1β and IL-18, actively involving in the innate immune responses of DED.
Conclusions :
These findings demonstrate collectively a critical role of caspase-8-inducing NLRP3 inflammasome activation in processing IL-1β and IL-18 maturation and decreasing the expression of NLRP6 in DED. These results provide new insight into the pathogenesis of DED and point to a treatment strategy.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.