Neuroprotective effects of voluntary exercise in an inherited retinal degeneration mouse model

Adam Hanif, Eric Lawson, Megan Prunty, Marissa Gogniat, Moe Aung, Ranjay Chakraborty, Jeffrey Boatright, Machelle Pardue

    Research output: Contribution to journalArticlepeer-review

    25 Citations (Scopus)

    Abstract

    Purpose: Our previous investigations showed that involuntary treadmill exercise is neuroprotective in a light-induced retinal degeneration mouse model, and it may act through activation of tropomyosin-related kinase B (TrkB) receptors. This study investigated whether voluntary running wheel exercise can be neuroprotective in an inheritable model of the retinal degenerative disease retinitis pigmentosa (RP), rd10 mice. Methods: Breeding pairs of rd10 and C57BL/6J mice were given free-spinning (active) or locked (inactive) running wheels. Pups were weaned into separate cages with their parents’ respective wheel types, and visual function was tested with ERG and a virtual optokinetic system at 4, 5, and 6 weeks of age. Offspring were killed at 6 weeks of age and retinal cross-sections were prepared for photoreceptor nuclei counting. Additionally, separate cohorts of active and inactive rd10 pups were injected daily for 14 days after eye opening with a selective TrkB receptor antagonist (ANA-12) or vehicle solution and assessed as described above. Results: Mice in the rd10 active group exhibited significant preservation of visual acuity, cone nuclei, and total photoreceptor nuclei number. Injection with ANA-12 precluded the preservation of visual acuity and photoreceptor nuclei number in rd10 mice. Conclusions: Voluntary running partially protected against the retinal degeneration and vision loss that otherwise occurs in the rd10 mouse model of RP. This protection was prevented by injection of ANA-12, suggesting that TrkB activation mediates exercise’s preservation of the retina. Exercise may serve as an effective, clinically translational intervention against retinal degeneration.

    Original languageEnglish
    Pages (from-to)6839-6846
    Number of pages8
    JournalInvestigative Ophthalmology and Visual Science
    Volume56
    Issue number11
    DOIs
    Publication statusPublished - 2015

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