June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Forced exercise paradigm promotes decreased recruitment of retinal inflammatory cells and protects against retinal degeneration
Author Affiliations & Notes
  • Hayden Haupt
    Atlanta VA Center for Visual & Neurocognitive Rehabilitation, Decatur, Georgia, United States
  • Katie Bales
    Atlanta VA Center for Visual & Neurocognitive Rehabilitation, Decatur, Georgia, United States
  • GianMarco Lee Douglas
    Atlanta VA Center for Visual & Neurocognitive Rehabilitation, Decatur, Georgia, United States
  • Joshua Chu-Tan
    Eccles Institute of Neuroscience, John Curtin School of Medical Research, Australian National University College of Health and Medicine, Canberra, Australian Capital Territory, Australia
    School of Medicine and Psychology, Australian National University College of Health and Medicine, Canberra, Australian Capital Territory, Australia
  • Riccardo Natoli
    Eccles Institute of Neuroscience, John Curtin School of Medical Research, Australian National University College of Health and Medicine, Canberra, Australian Capital Territory, Australia
    School of Medicine and Psychology, Australian National University College of Health and Medicine, Canberra, Australian Capital Territory, Australia
  • John N. Nickerson
    Ophthalmology, Emory University, Atlanta, Georgia, United States
  • Machelle T Pardue
    Atlanta VA Center for Visual & Neurocognitive Rehabilitation, Decatur, Georgia, United States
    Ophthalmology, Emory University, Atlanta, Georgia, United States
  • Jeffrey H Boatright
    Atlanta VA Center for Visual & Neurocognitive Rehabilitation, Decatur, Georgia, United States
    Ophthalmology, Emory University, Atlanta, Georgia, United States
  • Footnotes
    Commercial Relationships   Hayden Haupt None; Katie Bales None; GianMarco Douglas None; Joshua Chu-Tan None; Riccardo Natoli None; John Nickerson None; Machelle Pardue None; Jeffrey Boatright None
  • Footnotes
    Support  The Abraham J. and Phyllis Katz Foundation, NIH R01EY028859, R01EY028450, R01EY021592, R01EY031042, P30EY006360, VA IK6 RX003134, VA IK2BX005304, VA RR&D I01RX002806 and I50RX002358.
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 4485. doi:
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    • Get Citation

      Hayden Haupt, Katie Bales, GianMarco Lee Douglas, Joshua Chu-Tan, Riccardo Natoli, John N. Nickerson, Machelle T Pardue, Jeffrey H Boatright; Forced exercise paradigm promotes decreased recruitment of retinal inflammatory cells and protects against retinal degeneration. Invest. Ophthalmol. Vis. Sci. 2023;64(8):4485.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Our labs have demonstrated exercise is protective in animal models of retinal degeneration (RD). Retinal dysfunction is exacerbated by activation of immune pathways and recruitment of subretinal macrophages and or microglia. Here, we explore the effect of treadmill exercise on the recruitment of retinal inflammatory cells to the subretinal space in a light-induced retinal degeneration model (LIRD) that exhibits phenotypes found in patients with RD.

Methods : Adult male BALB/c mice were assigned to inactive (I)-dim, active (A)-dim, inactive (I)-LIRD and active (A)-LIRD groups (n=15 per group). Active mice were treadmill exercised (1hr/d, 10m/min) for two weeks, then LIRD was induced (5000 lux/4hrs). Inactive mice were placed on a static treadmill for the same schedule. At week three, retinal function was assessed using electroretinography (ERG). Tissues were collected 1 and 5-days post LIRD. Retinal sagittal sections were stained for inflammatory markers (Iba1, GFAP, CD11B), TUNEL (cell death), and photoreceptor nuclei (outer nuclear layer; ONL) were quantified. Data were analyzed using 2-way ANOVA.

Results : Dark-adapted a- and b-wave amplitudes were 1.98x (p<0.0093) and 1.72x (p<0.0004) greater in A-LIRD compared to I-LIRD mice, respectively. Retinal sections from A-LIRD mice had decreased presence of Iba1+ cells in the subretinal space (p<0.0001) and GFAP labeling (p<0.0001) 5-days post LIRD compared to I-LIRD mice. I-LIRD mice had increased presence of CD11B+ cells (p<0.0167) in the ONL 5-days post LIRD compared to A-LIRD. A-LIRD mice had decreased ONL TUNEL+ cells compared to I-LIRD both 1 and 5-days post LIRD (p<0.0007 and p<0.0001). I-LIRD mice showed a decline in ONL counts 1-day post LIRD with significant loss by 5 days post LIRD compared to A-LIRD mice (p<0.001).

Conclusions : Our results indicate treadmill exercise promotes preservation of photoreceptor function, decreased presence and or recruitment of inflammatory cells in the subretinal space and decreased photoreceptor cell death which results in photoreceptor nuclei preservation. These results suggest exercise can alter the recruitment or presence of inflammatory cells to the retina, which could provide insight for exercise-based therapies and treatments for RD and neuroinflammatory diseases.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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