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

• Type of Material: Article
• Authors: Adam M. Hanif, Atlanta VA Medical Center; Eric C. Lawson, Atlanta VA Medical Center; Megan Prunty, Atlanta VA Medical Center; Marissa Gogniat, Atlanta VA Medical Center; Moe H. Aung, Emory University; Ranjay Chakraborty, Emory University; Jeffrey Boatright, Emory University; Machelle Pardue, Emory University
• Language: English
• Date: 2015-10-01
• Publisher: Association for Research in Vision and Ophthalmology (ARVO)
• Publication Version: Final Published Version
• Copyright Statement: © 2015 The Association for Research in Vision and Ophthalmology, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1167/iovs.15-16792
• Title of Journal or Parent Work: Investigative Ophthalmology & Visual Science
• ISSN: 0146-0404
• Volume: 56
• Issue: 11
• Start Page: 6839
• End Page: 6846
• Grant/Funding Information: Supported by National Institutes of Health (Bethesda, MD, USA) Grants NIH P30 EY006360 (JHB/MTP) and NIH R01 EY014026 (JHB), and by a grant from the Abraham J. & Phyllis Katz Foundation (JHB; Atlanta, GA, USA).; This work was also supported by a Veterans Affairs Research Career Scientist Award (MTP; Washington, DC, USA), by the Atlanta VA Center of Excellence in Vision and Neurocognitive Rehabilitation Pilot Award (MTP/JHB; Atlanta, GA, USA), and by a departmental award from Research to Prevent Blindness (New York, NY, USA).
• Keywords: HIPPOCAMPAL FUNCTION; BDNF RECEPTOR; AEROBIC EXERCISE; NEUROTROPHIC FACTOR; Life Sciences & Biomedicine; LIGHT; retinal degeneration; TRKB; Ophthalmology; exercise; brain-derived neurotrophic factor; A-WAVE; BRAIN; RAT RETINA; MICE; Science & Technology
• Research Categories: Health Sciences, Rehabilitation and Therapy; Health Sciences, Opthamology

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.