Overexpression of membrane bound Fas ligand accelerates inflammation in response to corneal alkali burns.

Abstract

Purpose : The Fas/Fas ligand (FasL) system plays an integral role in the maintenance of corneal immune privilege and regulation of corneal wound healing. Previous research has shown that membrane bound FasL (mFasL) and soluble FasL (sFasL) exert opposing pro- and anti-inflammatory effects respectively in response to corneal injury. This study aims to explore the proinflammatory role of mFasL in the setting of alkali burns in mouse corneas which are sFasL deficient.

Methods : A mouse model with a deleted matrix metalloprotrease cleavage site was established to suppress the expression of sFasL, resulting in increased levels of mFasL expression systemically. To induce injury, the corneas were exposed to alkali burns. The corneas were observed for one month following injury to monitor for corneal neovascularization (CoNV), and then harvested. The collected corneas were stained for macrophage markers F4/80 and CD11b then analyzed and quantified by immunofluorescence.

Results : The mice that overexpressed mFasL showed significantly increased CoNV 14 days after alkali burn treatment compared with wild-type mice. Analysis of the harvested corneas from mFasL mice also showed an approximately 30% increase in F4/80+ and CD11b+ inflammatory cell infiltration at 1 month compared to the control group.

Conclusions : The increased CoNV and inflammatory cell infiltration observed in the corneas of mice that overexpressed mFasL suggests that mFasL plays a proinflammatory role in the cornea after injury. Considering the impact of mFasL on corneal injury and wound healing, it may serve as a potential target for therapy in corneal disease.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.