Abstract
Purpose :
Age-related macular degeneration (AMD) is one of the major causes of blindness in older veterans and the general US population. While exercise benefits retinal neurons, determining optimal exercise regimens for maximal benefit has been difficult as the mechanisms remain elusive. Here we explore a potential mechanism of exercise-induced retinal protection mediated by BDNF-enhanced retinal astrocyte plasticity using a light-induced retinal degeneration model (LIRD) that exhibits phenotypes found in patients with AMD.
Methods :
BALB/c mice were randomly assigned to active-dim, inactive-dim, inactive-LIRD and active-LIRD groups. Active mice were treadmill exercised 1hr/day at 10 meters/min for 2 weeks, then LIRD was induced with bright light exposure (4000 lux for 4 hours). Active groups were then exercised an additional week. Inactive controls were placed on static treadmills. Retinal function was assessed by electroretinography (ERG). Retinas were collected for western blots probing for BDNF and interleukin-6 (IL6) levels or were fixed to stain for glial fibrillary acidic protein (GFAP) and BDNF. Astrocytes were assessed for number/image and branching using Sholl and Skeletonize analyses. Statistical analyses performed were 2-way ANOVA with Tukey multiple comparisons test (mean±SEM).
Results :
LIRD decreased retinal function as measured by ERG. Importantly, retinal function in active-LIRD groups was significantly preserved compared to inactive-LIRD groups based on a-wave (active-LIRD:105.99±2.52μV;inactive-LIRD:45.96±11.3μV,p=0.041) and b-wave (active-LIRD:232.26±10.88μV;inactive-LIRD:74.07±17.77μV,p=0.003) amplitudes. Western blots revealed increased BDNF and decreased IL6 levels in active groups compared to inactive groups. Active-LIRD had increased astrocytes/image (active-LIRD:9.92±0.35; inactive-LIRD:4.38±0.29), and increased dendritic tips/cell and cellular branching (active-LIRD:93.4±3.47; inactive-LIRD: 40.95±4.40;p<0.0001).
Conclusions :
These results suggest that the protective effects of exercise on retinal degeneration may be due to BDNF signaling mediated by astrocytes, which show increased morphological complexity and branching after exercise treatment. These data align with reports that exercise-induced hippocampal synaptogenesis results from increased release of local BDNF leading to pro-neurogenic changes in astrocytic morphology and function.
This is a 2020 ARVO Annual Meeting abstract.