# Investigating the role of retinal astrocytes in exercise-induced retinal neuroprotection

> **NIH VA IK2** · VETERANS HEALTH ADMINISTRATION · 2024 · —

## Abstract

Photoreceptor dysfunction is one of the hallmark pathologies associated with retinal degenerative (RD)
diseases that manifests in patients as a progressive loss of vision. This encompasses heterogenous diseases
such as retinitis pigmentosa, which affects 1 in 3500 people worldwide and age-related macular degeneration,
which affects over 196 million people worldwide and is projected to reach 288 million people by 2040.
Specifically, in our Veteran population, roughly 7,000 Veterans become visually impaired each year due to RD.
Clinical trials and retrospective studies suggest that RD patients may respond to exercise as a neuroprotective
treatment to preserve vision. Recently, our labs filled a significant knowledge gap by demonstrating that
modest exercise protects retinal function and structure in models of RD and were accompanied by increased
levels of brain derived neurotrophic factor (BDNF) and required intact BDNF-TrkB signal transduction. To date,
the cell-types and molecular processes mediating the neuroprotective benefits of exercise are unknown.
Others have shown that astrocytes and endothelial cells in the brain express BDNF and its high-affinity
receptor, TrkB, and that altered BDNF-TrkB signaling in these cell-types contributes to neurodegenerative
disease progression and severity. Recently, it has been demonstrated that astrocytes modify their morphology
in response to BDNF in the brain during neurodegeneration. Likewise, vascular endothelial cells express BDNF
under exercise-induced physiological stress. These data suggest that astrocytes and endothelial cells may
mediate the neuroprotective effects of exercise in the retina. Our approach is to understand the morphological,
gene expression and functional alterations in retinal astrocytes and vasculature induced from exercise and how
these alterations contribute to neuroprotection. For this proposal, we will use the BALB/c light induced retinal
degeneration model, which exhibits phenotypes found in patients with RD. We hypothesize that exercise
induces retinal astrocyte plasticity and improved vascular function through increased BDNF signaling
mechanisms, promoting neural repair and protection. In Specific Aim 1, we will investigate if exercise
influences retinal astrocyte biology, by assessing retinal astrocyte morphology, cellular gene expression
profiles, and retinal astrocyte-mediated phagocytosis. Immunohistochemical labeling, AnalyzeSkeleton and
Sholl analysis will be used to quantify astrocyte cell morphology and density. Retinal astrocytes will be isolated
using magnetic-activated cell sorting (MACS) to examine astrocyte gene expression profiles. To monitor retinal
astrocyte function, a novel in vitro live-imaging of astrocyte-mediated phagocytosis will be used. In Specific
Aim 2, we will determine the effects of exercise on retinal vascular morphology, gene expression and function.
Angiotool will be used for retinal vascular morphology quantification analysis. Retinal vascula...

## Key facts

- **NIH application ID:** 10668348
- **Project number:** 5IK2BX005304-02
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** Katie Leigh Bales
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2022-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10668348

## Citation

> US National Institutes of Health, RePORTER application 10668348, Investigating the role of retinal astrocytes in exercise-induced retinal neuroprotection (5IK2BX005304-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10668348. Licensed CC0.

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