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.
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Authors | Adam M Hanif, Eric C Lawson, Megan Prunty, Marissa Gogniat, Moe H Aung, Ranjay Chakraborty, Jeffrey H Boatright, Machelle T Pardue |
Journal | Investigative ophthalmology & visual science
(Invest Ophthalmol Vis Sci)
Vol. 56
Issue 11
Pg. 6839-46
(Oct 2015)
ISSN: 1552-5783 [Electronic] United States |
PMID | 26567796
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- ANA 12 compound
- Azepines
- Benzamides
- Receptor, trkB
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Topics |
- Analysis of Variance
- Animals
- Azepines
(pharmacology)
- Benzamides
(pharmacology)
- Disease Models, Animal
- Electroretinography
- Mice
- Mice, Inbred C57BL
- Neuroprotection
(drug effects, physiology)
- Physical Conditioning, Animal
(physiology)
- Receptor, trkB
(antagonists & inhibitors, physiology)
- Retinal Cone Photoreceptor Cells
(cytology, drug effects, physiology)
- Retinal Rod Photoreceptor Cells
(cytology, drug effects, physiology)
- Retinitis Pigmentosa
(physiopathology, prevention & control)
- Visual Acuity
(physiology)
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