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

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.

• 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.)

Chemical References

• ANA 12 compound
• Azepines
• Benzamides
• Receptor, trkB

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)