Exercise-induced Retinal Neuroprotection

运动引起的视网膜神经保护

• 批准号: 10011820
• 负责人: JEFFREY H BOATRIGHT
• 金额: $ 49.8万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10011820
• 关键词: Address; Adult; Affect; Age; Age related macular degeneration; Aging; Alzheimer' 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' 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

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.

体育锻炼在正常健康的衰老过程中保护许多大脑区域， 神经退行性疾病，如阿尔茨海默病和帕金森病。然而， 运动对视网膜的影响是未知的，直到我们最近发表了令人兴奋的数据，表明适度的跑步机 跑步可以保护小鼠免受光诱导视网膜变性（LIRD）的影响，并且在rd 10小鼠模型中具有保护作用 视网膜色素变性在这里，我们建议使用视网膜的诱导和遗传模型来探索这种反应。 退化我们假设，运动对疾病中的视力结果有保护作用， 通过生物和分子机制衰老，这些机制与大脑中观察到的反应相似， 锻炼身体这将通过两个目标在一个简单的研究设计中进行测试： 在目标1中，我们将优化运动方案，以获得最大的保护。年轻（3个月大）和老年（12- 18月龄）小鼠将在不同持续时间、速度和敏捷度的跑步机上跑步。视网膜 损伤将诱发变性（例如，LIRD）或遗传性病变（例如，Tvrm 4小鼠模型 视网膜色素变性，代替RD 10小鼠）。这些实验将指导我们选择锻炼方式 在探索神经保护机制的方案。 在目标2中，我们将测试运动诱导的视网膜保护是否通过对视网膜的影响来调节。 炎症通路和能量稳态。我们的初步发现支持了脑源性 神经营养因子（BDNF）和抑制反应性胶质增生。我们将进一步研究视网膜神经营养素 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， 生物起源。最后，我们将测试运动是否对表现出高度炎症的老年小鼠具有保护作用。 对损伤和退化的反应。 运动简单、便宜，而且很多人都能做得到。它还具有额外的好处， 非视觉疾病。它应该很快就能转化为诊所。我们的实验将改变我们的基本 了解视网膜与身体其他部位的关系，就像类似的运动研究一样， 扩大我们对全身生理学对神经退行性疾病，衰老， 抑郁和认知。