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Vered Horwitz, Shlomit Dachir, Maayan Cohen, Hila Gutman, Liat Cohen, Eliezer Fishbine, Rachel Brandeis, Ariel Gore, Tamar Kadar; Biomarkers in the tear fluid during chemical ocular injury in the rabbit model. Invest. Ophthalmol. Vis. Sci. 2013;54(15):6034.
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Analysis of biomarkers in the tear fluid enables continuous follow-up during ocular pathologies. The sight threatening sulfur mustard (SM) induced ocular injury presents specific clinical symptoms for each injury stage. While the partially healed acute phase is characterized by erosions and severe inflammation, the permanent delayed pathology that is developed only in part of the eyes, is clinically expressed by epithelial defects and neovascularization (NV). The mechanisms underlying this injury are still in research and treatment is not sufficient. Aiming to improve the therapeutic strategies, we focused on finding biomarkers in the tear fluid that point out towards the pathological processes during the injury.
Rabbit eyes were exposed to SM vapor and a clinical follow-up was carried out up to 4 weeks. Tear fluid and corneal samples were collected at different time points and MMP-2 and MMP-9 activities were measured by zymography and VEGF, IL-8, IL-6, TNFα and IL-1β levels were measured by ELISA.
Typical SM-induced ocular injury was developed, including an acute phase that subsided within a week in all of the exposed eyes, followed by a permanent delayed pathology in 50%-80% of the eyes, beginning at 2w. In the tear fluid elevation in MMP-9 activity and IL-8 level was seen. While MMP-9 activity remained high throughout the follow-up period in all of the exposed eyes, IL-8 levels corresponded with the severity of the clinical symptoms. Interestingly, relatively higher IL-8 levels in tear fluid were noticed in future neovascularized eyes before NV appearance, indicating a role in prediction of the delayed pathology. IL-8 level and MMP-9 activity were elevated in the corneal tissue as well, indicating a possible source for these proteins in the tear fluid.
Biomarkers in the tear fluid are a sensitive tool for monitoring pathological mechanisms during the dynamic course of the ocular injury. These biomarkers can rationalize novel therapeutic strategies and serve as a tool for treatment evaluation. Moreover, IL-8 level in the tear fluid at the early stages of the injury may be indicative for the future injury outcome and the need for a preventive therapy.
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