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Tonia S Rex, Alexandra Bernardo-Colon, Victoria Vest, Adrienne Clark, Bohan Kim, John Clifton, Ryan Dahl, Fiona Harrison; The IL-1 pathway is a key mediator of axon degeneration and vision loss in a mouse model of indirect traumatic optic neuropathy.. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5514.
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The goal of this study was to determine if an antioxidant or ketogenic diet could prevent axon degeneration and vision loss in a mouse model of traumatic optic neuropathy.
Wild-type male C57Bl/6 mice were fed a high vitamin C and vitamin E (VitC/E) diet, a ketogenic diet, or control diets. Gulolactone oxidase knock-out (Gulo-/-) mice were maintained on a low vitamin C diet. Two weeks after initiation of the diets the left eyes were exposed to multiple 15psi air blasts. Optical coherence tomography and visual evoked potentials were performed at baseline and prior to collection at two or four weeks after injury. Retinal superoxide levels were quantified in vivo. Retinas, optic nerves, and brains were collected for biochemical and histological analysis to measure IL-1 pathway activation, axon degeneration in the optic nerve, and active anterograde axon transport to the superior colliculus.
The high VitC/E diet caused an increase in retinal levels of VitE. Both diets prevented an injury-induced increase in superoxide and levels of IL-1a, IL-1b, and cleaved caspase-1. Both diets preserved optic nerve histology and function after injury. Gulo-/- mice had lower tissue levels of VitC, high superoxide levels, and higher levels of IL-1 pathway proteins and greater axon degeneration and vision loss as compared to blast-injured control diet mice.
Trauma-induced oxidative stress activates the IL-1 pathway. Both a high antioxidant diet and a ketogenic diet prevent IL-1 pathway activation. Both diets prevent secondary axon degeneration and vision loss after indirect traumatic optic neuropathy. A potential therapeutic target is IL-1a, an alarmin, which is active and secreted even in its pro-form.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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