Abstract
Purpose :
Our labs have demonstrated exercise as a promising intervention in animal models of retinal degeneration (RD). Exercise-induced retinal protection was accompanied by increased levels of brain derived neurotrophic factor (BDNF) and required intact signaling via its high-affinity receptor, TrkB. In the brain, imbalances in astrocytic expression of BDNF and specific TrkB isoform expression, particularly increased TrkB.T1, contribute to neurodegeneration severity. Here, we explore the role of retinal astrocytes in exercise-induced retinal neuroprotection using a light-induced retinal degeneration model (LIRD) that exhibits phenotypes found in patients with RD.
Methods :
Adult male BALB/c mice were assigned to active(A)-dim, inactive(I)-dim, inactive(I)-LIRD and active(A)-LIRD groups (n=36 per group). Active mice were treadmill exercised (1hr/d, 10m/min) for two wks, then LIRD was induced (5000 lux/4hrs). Inactive groups were on a static treadmill for the same schedule. At week three, retinal function was assessed using ERG. Retinal flat mounts were stained for astrocytes (GFAP) and density, branching and dendritic arborization were quantified. Magnetic activated cell sorting (ACSA-2) and ddPCR was used to isolate retinal astrocytes and quantify gene expression of BDNF and various TrkB isoforms. Data were analyzed using 2-way ANOVA.
Results :
A-LIRD a- and b-wave mean amplitudes were 2.5x and 1.9x greater than I-LIRD means respectively (p<0.001), indicating that exercise significantly preserved retinal function. Flat mounts from A-LIRD mice had 50% more astrocytes (p<0.0001), 44% more branching (p<0.0001,) and 69% more arborization (p<0.05). Isolated retinal astrocytes from A-LIRD mice had increased TrkB.FL expression (p=0.006), I-LIRD mice had increased TrkB.T1 expression (p=0.014) and active groups had increased BDNF expression compared to inactive (p=0.025).
Conclusions :
Our results indicate exercise influences retinal astrocyte morphology and gene expression. Retinal astrocytes from A-LIRD groups showed increased expression of BDNF and TrkB.FL, the TrkB isoform associated with cell survival. These results suggest exercise can alter retinal astrocyte morphology and restore BDNF-TrkB signaling during RD, providing insight for exercise-based therapies for RD.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.