Exercise-induced Retinal Neuroprotection

体育锻炼在正常、健康的衰老过程中保护大脑的许多区域，并具有保护作用 神经退行性疾病，如阿尔茨海默病和帕金森病。然而，这一影响 直到我们最近发表了令人兴奋的数据，证明了适度的跑步机，视网膜上的运动才被发现 跑步保护小鼠免受光诱导视网膜变性(Lird)的影响，并在rd10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和疾病期间的视觉结果有保护作用。 通过与在大脑中观察到的反应相似的生物和分子机制来实现衰老 锻炼身体。这将在一个简单的研究设计中通过两个目标进行测试： 在目标1中，我们将优化运动养生方案，以实现最大限度的保护。年轻人(3个月大)和老年人(12- 18个月大的小鼠将在跑步机上跑步，跑步机的持续时间、速度和间歇性各不相同。视网膜 退化将由损伤(例如Lird)或由遗传损伤(例如Tvrm4小鼠模型)引起 视网膜色素变性，替代RD10小鼠)。这些实验将指导我们选择锻炼 在探索神经保护机制方面的养生法。 在目标2中，我们将测试运动诱导的视网膜保护是否与对视网膜的影响有关 炎症途径和能量动态平衡。我们的初步发现支持脑源性药物的作用 神经营养因子(BDNF)与反应性胶质增生的抑制。我们将进一步检查视网膜神经营养 我们将探讨运动对视网膜细胞因子通路和线粒体健康的影响。 生物发生学。最后，我们将测试运动对表现出高炎症反应的老年小鼠是否具有保护作用。 对损伤和退化的反应。 锻炼简单、便宜，而且很多人都能接受。它已经知道了额外的好处 非视力疾病。它应该很快就会被转移到诊所。我们的实验将从根本上改变我们的 了解视网膜与身体其他部分的关系，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、 抑郁症和认知力。

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.