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Brian Choi, Mark M Magharious, Philippe M D'Onofrio, Paulo D Koeberle; Treadmill exercise enhances retinal ganglion cell survival after axotomy. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2414.
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© ARVO (1962-2015); The Authors (2016-present)
The PI3K (Phosphatidylinositide-3 kinase) and MAPK (mitogen activated protein kinase) pathways are activated in the brain by exercise; these pathways are also important for RGC (retinal ganglion cell) survival following injury. This study investigated the effects of exercise on activation of PI3K and MAPK in the retina, and RGC survival after optic nerve transection.
Adult female Sprague-Dawley rats received optic nerve transections and RGCs were retrogradely labeled with Fluorogold. RGC survival was quantified at 14 days postaxotomy. Animals were exercised on a motorized treadmill to evaluate the activation of PI3K and MAPK pathways (n=6 for each group) or to examine the varying effects of light or heavy exercise (n=6 per condition). Light exercised animals were run for increasing distances and times over a 3 week period (totaling 150-600 m per day). Heavy exercise animals accumulated a total daily distance of 1320-1500 m over the 3 week span. Following training, animals were sacrificed and Western blots were used to assess the levels of Akt, phosphorylated Akt, MAPK, and phosphorylated MAPK. Separate groups of animals (n=6 per group) received exercise training for 2 weeks prior to optic nerve transection, and RGC survival was quantified at 7 and 14 days postaxotomy. Data was analyzed using a one-way ANOVA followed by Tukey’s post-hoc test in order to identify statistically significant differences between control and experimental groups.
Light exercise animals had lower levels of phosphorylated (activated) Akt compared to sedentary animals, with no change in phosphorylated MAPK. Heavily exercised animals did not show a significant difference in total or phosphorylated Akt or MAPK. At 14 days post-axotomy, the retinas of exercised animals had a significantly higher RGC density, compared to controls; RGC survival between groups was not significantly different at 7 days.
Exercise enhances RGC survival after injury, an effect that appears to be independent of PI3K or MAPK hyperphosphorylation that is associated with enhanced RGC survival after growth factor delivery.
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