title: Neuroprotective Effects of Voluntary Exercise in an Inherited Retinal Degeneration Mouse Model.
abstract: OBJECTIVE
  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.
authors.affiliation: Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, Georgia, United States.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Hanif
authors.affiliation: Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, Georgia, United States.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Lawson
authors.affiliation: Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, Georgia, United States.
authors.forename: Megan
authors.initials: M
authors.lastname: Prunty
authors.affiliation: Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, Georgia, United States.
authors.forename: Marissa
authors.initials: M
authors.lastname: Gogniat
authors.affiliation: Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia, United States.
authors.forename: Moe H
authors.initials: MH
authors.lastname: Aung
authors.affiliation: Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia, United States.
authors.forename: Ranjay
authors.initials: R
authors.lastname: Chakraborty
authors.affiliation: 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.
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Boatright
authors.affiliation: 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.
authors.forename: Machelle T
authors.initials: MT
authors.lastname: Pardue
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D004195:Disease Models, Animal; D004596:Electroretinography; D051379:Mice; D008810:Mice, Inbred C57BL; D000066829:Neuroprotection / Q000187:drug effects / Q000502:physiology*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D020813:Receptor, trkB / Q000037:antagonists & inhibitors / Q000502:physiology*; D017949:Retinal Cone Photoreceptor Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D017948:Retinal Rod Photoreceptor Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D012174:Retinitis Pigmentosa / Q000503:physiopathology* / Q000517:prevention & control; D014792:Visual Acuity / Q000502:physiology
chemical_list: C559317:ANA 12 compound; D001381:Azepines; D001549:Benzamides; D020813:Receptor, trkB