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Tonia S Rex, Alexandra Bernardo-Colon, Victoria Vest, Melissa Cooper, David J Calkins; Progression and pathology of blast-induced secondary indirect traumatic optic neuropathy. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4810. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To better understand the progression of secondary optic nerve degeneration after primary blast-injury.
We measured intraocular pressure and quantified axon degeneration, retinal ganglion cell death, anterograde axon transport, optic nerve glial morphometry, and levels of inflammatory proteins over time in the C57Bl/6 mouse after repeat exposure to eye-directed over-pressure air-waves (i.e. blasts).
Blast-exposure caused an immediate, but transient elevation in IOP. IL-1 family cytokines were elevated in the retina and optic nerve. Similar levels of axon degeneration were detected throughout the length of the optic nerve at all times assessed. Axon degeneration increased significantly at 2 days after the injury and again at 2-weeks after injury resulting in loss of 50% of axons at 1-month. Axon transport was initially decreased centrally and in the far periphery and the timing of transport deficits correlated with axon loss. Optic nerve glial hypertrophy was increased at 2 days and again at 1-month after injury. There was no change in glial parallelism or center of mass in the optic nerve at any time examined. Finally, there were many TUNEL-positive retinal ganglion cells at 10 days, fewer at 2-weeks, and none at 1-month post-blast.
Secondary neurodegeneration after blast appears to initiate in the retina with cell death occurring prior to axon degeneration. The extent of axon degeneration is greater than that seen in glaucoma models despite a lower IOP exposure suggesting a different mechanism of action. Further there was no distal to proximal progression of axon degeneration in blast-induced ITON. Early molecular events in blast-induced ITON include elevated oxidative stress and activation of the IL-1 pathway.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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