Abstract
Purpose :
The sight threatening sulfur mustard (SM) induced ocular injury presents specific symptoms for each clinical stage. The acute injury develops in all of the exposed eyes and is characterized by erosions and severe inflammation. The irreversible chronic pathology develops only in part of the eyes, and is clinically expressed by chronic inflammation and neovascularization (NV). The mechanisms underlying this injury are still in research and treatment is insufficient. Aiming to shed light on pathological mechanisms and improve the therapeutic strategies, we studied the expression pattern of various cytokines and chemokines at different clinical stages of the ocular injury.
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 IL-1α, IL-1β, IL-6, TNFα, macrophage chemotactic protein (MCP)-1 and IL-8 levels were measured by commercial ELISA kits.
Results :
Typical SM-induced ocular injury developed, including an acute injury that was partially resolved within a week in all of the exposed eyes, and followed by an irreversible chronic pathology in 50%-80% of the eyes, beginning at 2w. Significant elevations were seen in the 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 IL-1α, IL-8, and TNFα and limbal IL-1α and MCP-1 were found. At 1w, corneal IL-1β, IL-6, IL-8 and TNFα and limbal IL-8 and MCP-1 levels were significantly higher compared to naïve. During the chronic pathology, at 4w, elevated levels of corneal IL-1β, IL-6 and MCP-1 and limbal MCP-1 and IL-8 were found only in eyes presenting NV.
Conclusions :
The levels of the studied factors changed throughout the dynamic course of the ocular injury. The prolonged increased levels of limbal MCP-1 and IL-8 may contribute to the continuous recruitment of inflammatory cells, characterizing the chronic pathology. Higher levels of corneal IL-1α and TNFα were seen during the peak of the acute injury, while elevated expression of corneal MCP-1, IL-6 and IL-1β characterized the chronic pathology. Mapping the expression pattern of these cytokines and chemokines points out towards stage-specific therapeutic options.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.