Exacerbation of blast-induced ocular trauma by an immune response.

Abstract

BackgroundVisual prognosis after an open globe injury is typically worse than after a closed globe injury due, in part, to the immune response that ensues following open globe trauma. There is a need for an animal model of open globe injury in order to investigate mechanisms of vision loss and test potential therapeutics.MethodsThe left eyes of DBA/2 J mice were exposed to an overpressure airwave blast. This strain lacks a fully functional ocular immune privilege, so even though the blast wave does not rupture the globe, immune infiltrate and neuroinflammation occurs as it would in an open globe injury. For the first month after blast wave exposure, the gross pathology, intraocular pressure, visual function, and retinal integrity of the blast-exposed eyes were monitored. Eyes were collected at three, seven, and 28 days to study the histology of the cornea, retina, and optic nerve, and perform immunohistochemical labeling with markers of cell death, oxidative stress, and inflammation.ResultsThe overpressure airwave caused anterior injuries including corneal edema, neovascularization, and hyphema. Immune infiltrate was detected throughout the eyes after blast wave exposure. Posterior injuries included occasional retinal detachments and epiretinal membranes, large retinal pigment epithelium vacuoles, regional photoreceptor cell death, and glial reactivity. Optic nerve degeneration was evident at 28 days post-blast wave exposure. The electroretinogram (ERG) showed an early deficit in the a wave that recovered over time. Both visual acuity and the ERG b wave showed an early decrease, then a transient improvement that was followed by further decline at 28 days post-blast wave exposure.ConclusionsOcular blast injury in the DBA/2 J mouse recapitulates damage that is characteristic of open globe injuries with the advantage of a physically intact globe that prevents complications from infection. The injury was more severe in DBA/2 J mice than in C57Bl/6 J mice, which have an intact ocular immune privilege. Early injury to the outer retina mostly recovers over time. In contrast, inner retinal dysfunction seems to drive later vision loss.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-014-0192-5) contains supplementary material, which is available to authorized users.