Treadmill exercise promotes retinal astrocyte plasticity and protects against retinal degeneration in a mouse model of light-induced retinal degeneration

• Authors: Katie L Bales, Atlanta VA Center for Visual and Neurocognitive Rehabilitation; Alicia S Chacko, Atlanta VA Center for Visual and Neurocognitive Rehabilitation; John Nickerson, Emory University; Jeffrey Boatright, Emory University; Machelle Pardue, Emory University
• Journal Title: JOURNAL OF NEUROSCIENCE RESEARCH
• Volume: Volume 100, Number 9
• Publisher: WILEY | 2022-05-18, Pages 1695-1706
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1002/jnr.25063
• Subjects: Engineering, Biomedical
• Keywords: Science & Technology; Life Sciences & Biomedicine; Neurosciences; Neurosciences & Neurology; aerobic exercise; light damage model; retina; retinal neuroprotection; RRID; AB_880202; AB_788229; AB_2039891; AB_2534102; AB_2894998; NEUROTROPHIC FACTOR; MACULAR DEGENERATION; PHYSICAL-ACTIVITY; BDNF; AGE; NEUROPROTECTION; DEATH; CELLS; GLIA

Abstract

Exercise is an effective neuroprotective intervention that preserves retinal function and structure in several animal models of retinal degeneration. However, the retinal cell types governing exercise-induced neuroprotection remain elusive. Previously, we found exercise-induced retinal neuroprotection was associated with increased levels of retinal brain-derived neurotrophic factor (BDNF) and required intact signal transduction with its high-affinity receptor, tropomyosin kinase B (TrkB). Brain studies have shown astrocytes express BDNF and TrkB and that decreased BDNF–TrkB signaling in astrocytes contributes to neurodegeneration. Additionally, exercise has been shown to alter astrocyte morphology. Using a light-induced retinal degeneration (LIRD) model, we investigated how exercise influences retinal astrocytes in adult male BALB/c mice. Treadmill exercise in dim control and LIRD groups had increased astrocyte density, GFAP labeling, branching, dendritic endpoints, and arborization. Meanwhile, inactive LIRD animals had significant reductions in all measured parameters. Additionally, exercised groups had increased astrocytic BDNF expression that was visualized using proximity ligase assay. Isolated retinal astrocytes from exercised LIRD groups had significantly increased expression of a specific isoform of TrkB associated with cell survival, TrkB.FL. Conversely, inactive LIRD isolated retinal astrocytes had significantly increased expression of TrkB.T1, which has been implicated in neuronal cell death. Our data indicate exercise not only alters retinal astrocyte morphology but also promotes specific BDNF–TrkB signaling associated with cell survival and protection during retinal degeneration. These findings provide novel insights into the effects of treadmill exercise on retinal astrocyte morphology and cellular expression, highlighting retinal astrocytes as a potential cell type involved in BDNF–TrkB signaling.