Abstract
Purpose :
The sight threatening sulfur mustard (SM) induced ocular injury presents specific symptoms for each clinical stage. While the acute injury is characterized by erosions and severe inflammation, the chronic or late pathology that develops only in part of the eyes, is clinically expressed by corneal epithelial defects and neovascularization (NV). The pathological mechanisms underlying this injury are still under research and treatment is insufficient. Based on the results of RNA sequencing of corneas at 4 weeks post exposure, 5 mRNAs that were significantly elevated and were not studied previously in the context of SM-induced ocular injury were selected for further research. The expression pattern in both the cornea and the limbus at additional time points during the course of the injury was studied in the rabbit model.
Methods :
Rabbit eyes were exposed to SM vapor and a clinical follow-up was carried out up to 4 weeks. Corneal and limbal tissues were collected at 48h, 1w and 4w post exposure and MMP-1, MMP-10, IRS-1, NGF and IL-33 mRNA levels were measured using real time PCR.
Results :
Typical SM-induced ocular injury developed, including an acute injury that was partially resolved within a week in all of the exposed eyes, followed by an irreversible late pathology in 50%-80% of the eyes, beginning at 2w. Significant elevations were seen in the mRNA levels of the studied factors, however each factor presented a unique expression pattern. At the peak of the acute injury, at 48 h, significantly higher levels of corneal and limbal MMP-1, MMP-10 and NGF and corneal IRS-1 were found. At 1w, corneal and limbal MMP-1 and MMP-10 and corneal NGF, IRS-1 and IL33 levels were significantly elevated compared to naïve. During the late pathology, at 4w, significantly higher levels of corneal MMP-1, MMP-10, NGF and IRS-1 were found, with no change in the limbal levels.
Conclusions :
The mRNA levels of the studied factors changed throughout the dynamic clinical course of the ocular injury and between the cornea and the limbus, mainly during the late pathology. The results suggest a possible involvement of these factors in the pathological processes in different ocular tissues at specific stages of the injury and may point out towards stage-specific therapeutic options.
This is a 2021 ARVO Annual Meeting abstract.