July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Exercise protects against retinal degeneration and retinal pigment epithelium (RPE) stress in the RHOtvrm4/+ mouse model of retinitis pigmentosa
Author Affiliations & Notes
  • Xian Zhang
    Ophthalmology, Emory University, Atlanta, Georgia, United States
    Ophthalmology, Second Xiangya Hospital of Central South University, Changsha, Hunan, China
  • Preston Girardot
    Ophthalmology, Emory University, Atlanta, Georgia, United States
  • Jana T Sellers
    Ophthalmology, Emory University, Atlanta, Georgia, United States
  • Wenfei Wu
    Ophthalmology, Emory University, Atlanta, Georgia, United States
    The First Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an, Shan'xi, China
  • Henry Skelton
    Morehouse School of Medicine, Atlanta, Georgia, United States
  • John M Nickerson
    Ophthalmology, Emory University, Atlanta, Georgia, United States
  • Machelle T Pardue
    Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, Georgia, United States
    Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States
  • Jeffrey H Boatright
    Ophthalmology, Emory University, Atlanta, Georgia, United States
    Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, Georgia, United States
  • Footnotes
    Commercial Relationships   Xian Zhang, None; Preston Girardot, None; Jana Sellers, None; Wenfei Wu, None; Henry Skelton, None; John Nickerson, None; Machelle Pardue, None; Jeffrey Boatright, None
  • Footnotes
    Support  R01 EY030357; Abraham J and Phyllis Katz Foundation (JHB); NIH R01EY028859 (JHB); NIH R01EY021592 (JMN); NIH R01EY028450 (JMN); VA I01RX002806 (JHB); VA I21RX001924 (JHB); VA RR&D C9246C (Atlanta VAMC) ; NIH P30EY06360 (Emory); VA Research Career Scientist Award IK6 RX003134 (MTP); Research to Prevent Blindness (Emory)
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 2354. doi:https://doi.org/
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    • Get Citation

      Xian Zhang, Preston Girardot, Jana T Sellers, Wenfei Wu, Henry Skelton, John M Nickerson, Machelle T Pardue, Jeffrey H Boatright; Exercise protects against retinal degeneration and retinal pigment epithelium (RPE) stress in the RHOtvrm4/+ mouse model of retinitis pigmentosa. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2354. doi: https://doi.org/.

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

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Abstract

Purpose : We find that modest running exercise protects photoreceptors in mouse models of retinal degeneration. Here we tested whether exercise similarly protects retinal pigment epithelium (RPE) cells undergoing stress observed weeks after activation of the RHOtvrm4/+ model of retinal degeneration.

Methods : Adult male RHOtvrm4/+ mice were given access to free spinning (active) or locked (inactive) running wheels. Two weeks later, half of each cohort was treated with 0.2% atropine eye drops and exposed to LED light (6,000 lux) for 5 minutes. Before light exposure and at 1 and 2 months after light exposure, optical coherence tomography (OCT), electroretinogram (ERG), and optomotor response (OMR) were assessed. Mice were then sacrificed and eyes fixed for flatmounting. Flatmounts were stained for ZO-1 and α-catenin to assess RPE cell structure and stress. (We previously reported that translocation of α-catenin from cell membranes into the cytosol indicates cell stress.)

Results : Activation of the RHOtvrm4/+ degeneration decreased visual acuity, thickness of the photoreceptor layer, and visual function. Notably, increased α-catenin translocation was observed in RPE flatmounts. These outcomes were partially prevented in exercised mice. Visual acuity (assessed as spatial frequency in units of cycles/degree) was significantly decreased in induced mice (0.108±0.049) compared to uninduced mice (0.274±0.022); p=0.01 by one-way ANOVA test, but exercise prevented this loss (0.211±0.016), observed as no significant difference with uninduced animals. Whole retina and photoreceptor layers as measured by OCT were significantly thicker in induced animals that were exercised versus non-exercised (138.6±9.00 vs 102.5±5.10; p=0.006) and 44.98±9.47 vs 11.59±3.81; p=0.009, respectively). Exercised mice did not exhibit increased RPE α-catenin translocation. ERG amplitudes trended towards less functional loss in exercised animals.

Conclusions : Activated RHOtvrm4/+ mice lose retinal and visual function, with concomitant changes in the morphology of the retina and RPE. Exercise significantly protects against this pathological process, observed as decreased RPE stress and better retinal and visual outcomes.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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