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Jessica Hernandez, Matthew Aaron Reilly, Walter Gray, Brian Lund, William Eric Sponsel, Randolph D Glickman, Sub-lethal ocular trauma; Ocular Trauma-Induced Changes in Aqueous and Plasma Biomarker Expression Levels. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):6026.
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© ARVO (1962-2015); The Authors (2016-present)
The wider use of explosive weapons has led to an increasing number of eye injuries sustained by U.S. military personnel during recent conflicts. This study was undertaken with the dual goals of better understanding the cellular and molecular responses to these injuries, and developing specific diagnostic indicators of ocular injury, by identifying trauma-related biomarkers in the aqueous humor and blood plasma of 23 rabbits subjected to moderate levels of blast overpressure (BOP).
Rabbits were anesthetized with ketamine/xylazine and subjected to BOP of 8, 12, and 17 psi, using a pressure-driven shock tube. Samples of aqueous humor (~100 µl) and blood (2 ml) were collected from rabbits before the blast and at 3 h, 24 h, and 48 h post-blast. The samples were analyzed using two Milliplex panels: the human neurodegenerative disorders kit (HND1MAG-39K) and the rat cytokine/chemokine kit (RECYMAG65K27PMX). The panels were selected on the basis of pre-assay cross-species reactivity tests. The panels were assayed using the Luminex xMAP 3D protocol. Statistical analysis by ANOVA was performed to determine significance of biomarker differences pre- and post-blast.
Cytokines and other protein markers that exhibited significant changes, associated with blast trauma, were found in both aqueous (Table 1A) and serum (Table 1B), in particular NSE, NGF-b, MIP-2, GM-CSF, and Phospho-tau (Figure 1). Several of these markers showed concentration changes that were positively or negatively correlated with blast intensity, e.g. NGF-b and MIP-2, respectively. Several of the biomarkers exhibited a progressive increase over 48 h, notably GM-CSF, MIP-2, and GRO/KC.
Molecular biomarkers associated with physical trauma were found in the aqueous humor and serum of animals subjected to BOP. Although some of these biomarkers have been reported after traumatic brain injury; there is little previous data relating these specifically to ocular trauma. In our related studies, we have found injuries to cornea and retina resulting from primary blast, and these tissues may be the source of some of these proteins. Understanding biomarkers associated with ocular trauma may provide the basis for better diagnostic tests and assessment of treatments for blast injury to the eye.
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