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Invest Ophthalmol Vis Sci. 2015 Oct;56(11):6839-46. doi: 10.1167/iovs.15-16792.

Neuroprotective Effects of Voluntary Exercise in an Inherited Retinal Degeneration Mouse Model.

Author information

1
Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, Georgia, United States.
2
Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia, United States.
3
Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, Georgia, United States 2Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia, United States.

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.

PMID:
26567796
PMCID:
PMC4627249
DOI:
10.1167/iovs.15-16792
[Indexed for MEDLINE]
Free PMC Article

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