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Eric Lawson, Moon Han, Jana Sellers, Micah Chrenek, Serena Jafer, Jeffrey Boatright, Machelle Pardue; Aerobic Exercise Preserves Retinal Function and Structure in Light Induced Retinal Degeneration Model. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1269.
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© ARVO (1962-2015); The Authors (2016-present)
Environmental enrichment (EE), which includes the use of a running wheel (aerobic exercise), has been shown to promote positive visual outcomes in retinal degenerative models. Here, we test whether aerobic exercise (AE) alone preserves retinal function and structure in the light-induced retinal degeneration (LIRD) mouse. We also examined possible mechanisms of action through the upregulation of brain derived neurotrophic factor (BDNF) and activation of the leukemia inhibitory factor (LIF) pathway.
BALB/c mice (10 wks old; maintained on a 12:12 hour light/dark cycle of 25 lux) were randomly assigned to 4 treatment groups: dim, active; dim, inactive; bright, active; or bright, inactive. Active mice were exercised on a treadmill 5 days/week for 60min at 10m/min for two weeks. Inactive mice were placed on the treadmill while it wasn’t operating. Following 2 weeks of exercise, mice were exposed to 4 hours of 25 lux or 10,000 lux white light. Mice were then exercised for 2 additional weeks. Retinal function was assessed using electroretinography (ERG) at 1 and 2 weeks post-light exposure. Structural changes were assessed as outer nuclear layer (ONL) cell counts on toluidine blue stained plastic retinal sections. Retina and serum BDNF levels were assessed using a BDNF enzyme-linked immunosorbent assay (ELISA). Additional retina samples were assessed for levels of LIF and heme oxygenase (decycling) 1 (HMOX1) using qRT-PCR.
Bright, active mice exhibited a significantly larger a- and b-wave response with a 145% and 106% greater max amplitudes, respectively, at the brightest flash stimulus compared to bright, inactive mice at both 1 and 2 weeks post-LIRD (p<0.001). Bright, active mice had 32% more photoreceptor nuclei superiorly to inferiorly across the retina compared to bright, inactive mice (p<0.001). Retina and serum protein extract from bright, active mice showed significantly greater levels of BNDF protein compared to bright, inactive mice (p=0.0239). Additionally, HMOX1 and LIF expression in bright, active retinas increased relative to bright, inactive by 73% and 168%, respectively.
Aerobic exercise alone protects retinal function and morphology in a retinal degeneration model. This is accompanied by elevated retinal and serum BDNF and upregulation of stress response genes LIF and HMOX1.
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