Abstract
Purpose :
Dry eye disease (DED) is a multifactor-induced autoimmune ocular surface disease characterized by discomfort, visual disturbance, and tear film instability. The exact pathogenesis of dry eye disease remains unclear. Therefore, this study aimed to investigate the potential mechanisms linking pyroptosis and necroptosis of corneal epithelial cells in response to environmental stress.
Methods :
An experimental DED model was built by subcutaneous injection of scopolamine and exposure to a desiccating environment of C57BL/6J mice and genetic mice on the background of C57BL/6J mice. The phenol red thread tear test and corneal epithelial defects evaluation were used to assess the severity of DED. Quantitative Real-time PCR, western blotting, and immunofluorescence staining were used to reflect the expression of protein factors in this study.
Results :
The study findings revealed increased levels of genes and proteins associated with necroptosis, namely RIP1, RIP3, and MLKL, in the DED model. These molecules were found to have regulatory effects on the inflammasome NLRP1 and NLRP12. Additionally, the genetic deletion of Caspase-1 and GSDMD, which are key molecules involved in pyroptosis, significantly reduced the expression of P-RIP3 and P-MLKL in dry eye.
Conclusions :
These findings suggest that RIP3/MLKL-mediated necroptosis is a significant factor in the development of DED. Additionally, caspase-1 enhances the occurrence of RIP3/MLKL-mediated necroptosis in corneal epithelial cells by cleaving GSDMD. It demonstrates that inflammation resulting from pyroptosis can exacerbate necroptosis, leading to damage in corneal tissue.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.