Abstract
Purpose :
The neuroprotective effects of exercise in regions of the central nervous system have been well documented, although the underlying molecular mechanisms remain elusive. We previously demonstrated that exercise is also protective to the degenerating retina. Here we explore the potential role of retinal astrocytes as mediators of exercise-induced retinal neuroprotection using a light-induced retinal degeneration model (LIRD) that exhibits phenotypes found in patients with retinal degenerations.
Methods :
Male adult BALB/c mice (n=48) were assigned to active(A)-dim, inactive(I)-dim, inactive (I)-LIRD and active (A)-LIRD groups. Active mice were exercised on a treadmill (1 hr/d at 10 m/min) for two weeks, then LIRD was induced with bright light exposure (4000 lux for 4 hrs). Active groups were exercised an additional week. Inactive controls were placed on static treadmills for the same duration and schedule. At week three, retinal function was assessed using electroretinography (ERG). One week after LIRD, retinal flat mounts were stained for astrocytes using GFAP and quantitatively assessed using Skeletonize analyses (ImageJ) for population density, and GFAP expression and Sholl analyses for astrocytic branching and dendritic arborization. A proximity ligase assay (PLA) was used to detect astrocyte and brain-derived neurotrophic factor (BDNF) interaction in active groups compared to inactive groups. Data were analyzed by 2-way ANOVA (mean±SEM).
Results :
LIRD diminished retinal function as measured by ERG. Importantly, retinal function in A-LIRD groups were significantly preserved compared to I-LIRD groups based on a-wave (p=0.041) and b-wave (p=0.003) amplitudes. Retinal flat mounts from A-LIRD mice had more astrocytes (A-LIRD: 9.00±0.35; I-LIRD: 4.00±0.29 # of cells per image) and cellular branching (A-LIRD: 93.4±3.47; I-LIRD: 40.95±4.40[PM1] # branches per cell; p<0.0001). PLA showed increased cellular interaction between GFAP and BDNF in retinas from active groups compared to inactive groups.
Conclusions :
Our results suggest that the protective effects of exercise on retinal degeneration may be due to BDNF signalingmediated by astrocytes. These studies provide important insights into the molecular mechanisms that govern exercise-induced retinal neuroprotection. This information may be useful in optimizing exercise interventions for patients with progressive retinal degenerations.
This is a 2021 ARVO Annual Meeting abstract.