Hanif Adam M, Lawson Eric C, Prunty Megan, Gogniat Marissa, Aung Moe H, Chakraborty Ranjay, Boatright Jeffrey H, Pardue Machelle T
Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, Georgia, United States.
Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia, United States.
Invest Ophthalmol Vis Sci. 2015 Oct;56(11):6839-46. doi: 10.1167/iovs.15-16792.
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.
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.
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.
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.
我们之前的研究表明，在光诱导视网膜变性小鼠模型中，非自愿跑步机运动具有神经保护作用，其可能通过激活原肌球蛋白相关激酶B（TrkB）受体发挥作用。本研究调查了自愿转轮运动在视网膜退行性疾病视网膜色素变性（RP）的遗传模型rd10小鼠中是否具有神经保护作用。
将rd10小鼠和C57BL/6J小鼠的繁殖对给予自由旋转（活动）或锁定（不活动）的转轮。幼崽断奶后与父母各自的转轮类型一起放入单独的笼子中，并在4、5和6周龄时用视网膜电图（ERG）和虚拟视动系统测试视觉功能。子代在6周龄时处死，制备视网膜横断面用于光感受器细胞核计数。此外，对单独一组睁眼后14天的活动和不活动的rd10幼崽每天注射选择性TrkB受体拮抗剂（ANA-12）或溶剂，并按上述方法进行评估。
rd10活动组小鼠的视力、视锥细胞核和总的光感受器细胞核数量得到了显著保留。注射ANA-12可阻止rd10小鼠视力和光感受器细胞核数量的保留。
自愿跑步部分预防了RP的rd10小鼠模型中否则会发生的视网膜变性和视力丧失。注射ANA-12可阻止这种保护作用，表明TrkB激活介导了运动对视网膜的保护作用。运动可能作为一种有效的、可临床转化的针对视网膜变性的干预措施。
