ABS 003: Exercise-Induced Alterations on Visual Cortex in a Light-Induced Retinal Degeneration Model

Jackson A. Banks ¹ ² Machelle T. Pardue ¹ ² ³ , Katie L. Bales ²

¹ Department of Biomedical Engineering at Georgia Institute of Technology and Atlanta VA Center for Visual and Neurocognitive Rehabilitation
² Atlanta VA Center for visual and Neurocognitive Rehabilitation, Department of Biomedical Engineering at Georgia Institute of Technology
³ Emory University School of Medicine

Van Wickle (2025) Volume 1, ABS 003

Introduction: One of the leading causes of vision loss in older adults is Age-Related Macular Degeneration (AMD) which is caused by the degeneration of retinal cell-types driven by inflammation. This loss of vision can also be reflected in neuronal and inflammatory alterations in the visual cortex. In the retina, exercise has been shown to modulate the inflammatory response, potentially slowing down retinal degeneration; however, there is still ambiguity about the effect of exercise on the visual cortex in AMD patients. The motivation for this study is to understand the role physical exercise has on chemokine/cytokine response and microglia morphology within the visual cortex in a mouse model of light-induced retinal degeneration (LIRD). Mice were divided into exercise and non-exercise groups, and quantifications were assessed comparing all experimental groups. Molecular and structural assessments were performed to quantify differences between groups include cytokine/chemokine expression assay and immunofluorescence to quantify microglia morphology. By evaluating the influence exercise has on the inflammatory response in the visual cortex of retinal degeneration models, there is potential for further examinations of economically effective and non-invasive interventions to maintain visual utility in patients with AMD. Additionally, the results of this study can contribute to the advancement of physical therapeutic techniques and regimens for AMD patients in the goal of the enhancement of quality of life through neurological health.

Methods: Adult BALB/c mice were divided into four groups: inactive+dim, active+dim, inactive+LIRD, and active+LIRD (n=5-7 per group). Mice in active groups exercised using treadmill or running wheels for three weeks, while inactive groups had locked wheels or static treadmills. Light-induced retinal degeneration (LIRD) was induced with toxic LED light exposure. Visual cortex tissue was collected and analyzed. Multiplex cytokine assays quantified inflammatory marker expression, and immunofluorescence was used to evaluate microglial morphology. Cytokine data were normalized and analyzed via two-way ANOVA with Tukey’s post hoc tests; microglial morphological data were evaluated using one-way ANOVA with Geisser-Greenhouse correction. Data were presented as mean ± SEM, and outliers were detected and excluded using the ROUT method (Q=1%).

Results: Exercise influenced cytokine expression and microglial morphology in the visual cortex. Several cytokines, including IFN-alpha, CXCL-1, Eotaxin, IL-2, and IL-6, showed significant alterations in active+LIRD animals compared to inactive controls. Microglial cells from exercised animals exhibited decreased branching, endpoints, and junctions relative to inactive animals, particularly in the LIRD groups. These findings suggest that exercise modulates inflammatory signaling and reduces microglial reactivity within the visual cortex under retinal degeneration stress.

Discussion: This study demonstrated that exercise modifies inflammatory cytokine profiles and microglial morphology in the visual cortex during retinal degeneration. Reduced pro-inflammatory cytokine expression and simpler microglial morphology in exercised animals suggest exercise suppresses neuroinflammation and may promote neuroprotection. These findings highlight the potential of physical exercise as a non-invasive strategy to preserve visual cortex integrity in degenerative retinal diseases. Future studies should examine additional visual cortex regions and molecular mechanisms underlying these protective effects.