Exercise-induced Retinal Neuroprotection

运动引起的视网膜神经保护

基本信息

批准号：
10238783
负责人：
JEFFREY H BOATRIGHT
金额：
$ 48.31万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-30 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10238783
关键词：
Address Adult Affect Age Age related macular degeneration Aging Alzheimer&apos s Disease Biogenesis Biological Brain Brain region Brain-Derived Neurotrophic Factor Clinic Clinical Trials Cognition Coupling Cytokine Receptors Cytokine Signaling Data Development Disease Dose Etiology Exercise Exhibits Genetic Gliosis Health Hippocampus (Brain)Homeostasis Inflammation Inflammatory Response Inherited Intervention Knowledge Lesion Light Mediating Mental Depression Microglia Mitochondria Modeling Molecular Monitor Muller&apos s cell Mus Neurodegenerative Disorders Neurons Neurotrophic Tyrosine Kinase Receptor Type 2 Outcome Parkinson Disease Pathology Pathway interactions Patients Photoreceptors Physical Exercise Physical activity Physiology Publishing Quality of life Receptor Activation Research Design Rest Retina Retinal Degeneration Retinitis Pigmentosa Retrospective Studies Rhodopsin Role Running Schedule Serum Signal Pathway Signal Transduction Speed Testing Transgenic Mice Translating Vision Visual Visual impairment Visually Impaired Persons aged biological adaptation to stress cost cytokine exercise regimen experimental study healthy aging improved member mouse model mutant neuroprotection protective effect response response to injury treadmill virtual

项目摘要

Physical exercise protects many brain regions during normal, healthy aging and is protective in neurodegenerative diseases such as Alzheimer disease and Parkinson disease. However, the effect of exercise on retina was unknown until we recently published exciting data demonstrating that modest treadmill running protects mice from light-induced retinal degeneration (LIRD) and is protective in the rd10 mouse model of retinitis pigmentosa. Here we propose to explore this response using induced and inherited models of retina degeneration. We hypothesize that exercise has protective effects on visual outcomes in disease and during aging through biological and molecular mechanisms that are similar to those observed in the brain in response to exercise. This will be tested in a straightforward research design via two aims: In Aim 1, we will optimize exercise regimens for greatest protection. Young (3 month old) and old (12- 18 months old) mice will be run on treadmills with varying duration, speed, and intermittency. Retinal degeneration will be induced by damage (e.g., LIRD) or by genetic lesions (e.g., the Tvrm4 mouse model of retinitis pigmentosa, in replacement of rd10 mice). These experiments will guide our choice of exercise regimen in exploring the mechanisms underlying neuroprotection. In Aim 2, we will test whether exercise-induced retinal protection is meditated by effects on retinal inflammation pathways and energy homeostasis. Our initial findings support a role for brain-derived neurotrophic factor (BDNF) and suppression of reactive gliosis. We will further examine retinal neurotrophic pathways and we will explore the effect of exercise on retinal cytokine pathways and mitochondrial health and biogenesis. Finally, we will test whether exercise is protective in aged mice that exhibit a hyper-inflammatory response to injury and degeneration. Exercise is simple, inexpensive, and accessible to many people. It has known additional benefits to non-visual diseases. It should translate quickly to the clinic. Our experiments will change our fundamental understanding of the relationship of the retina to the rest of the body, just as similar exercise studies are expanding our understanding of the effects of whole-body physiology on neurodegenerative disease, aging, depression, and cognition.

体育锻炼可以保护正常，健康衰老的许多大脑区域，并且具有保护性神经退行性疾病，例如阿尔茨海默氏病和帕金森病。但是，在视网膜上的练习是未知的，直到我们最近发布了令人兴奋的数据，证明了适度跑步可保护小鼠免受光引起的视网膜变性（lird），并在RD10鼠标模型中具有保护性色素性视网膜炎。在这里，我们建议使用视网膜的诱导和继承模型探索这一响应退化。我们假设运动对疾病的视觉结果和期间具有保护作用通过生物学和分子机制衰老，与大脑中观察到的相似锻炼。这将通过两个目的在直接的研究设计中进行测试：在AIM 1中，我们将优化运动方案，以提供最大的保护。年轻（3个月大）和老（12- 18个月大的）小鼠将以不同的持续时间，速度和间歇性不同的跑步机进行运行。视网膜变性将由损害（例如鳞茎）或遗传病变诱导（例如，TVRM4小鼠模型色素性视网膜炎，替代RD10小鼠）。这些实验将指导我们选择运动探索神经保护基础机制的方案。在AIM 2中，我们将测试运动引起的视网膜保护是否受到视网膜影响的影响炎症途径和能量稳态。我们的最初发现支持大脑衍生的角色神经营养因子（BDNF）和反应性神经胶质病的抑制。我们将进一步检查视网膜神经营养途径，我们将探讨运动对视网膜细胞因子途径和线粒体健康的影响生物发生。最后，我们将测试表现出高炎症的老年小鼠运动是否具有保护性对伤害和变性的反应。锻炼很简单，便宜，而且许多人都可以访问。它已经知道其他好处非视觉疾病。它应该迅速转化为诊所。我们的实验将改变我们的基本了解视网膜与身体其余部分的关系，就像类似的运动研究一样扩展我们对全身生理学对神经退行性疾病，衰老的影响的理解抑郁和认知。