Exercise-induced Retinal Neuroprotection

体育锻炼可以在正常、健康的衰老过程中保护许多大脑区域，并在 神经退行性疾病，例如阿尔茨海默病和帕金森病。然而，效果 直到我们最近发布了令人兴奋的数据，证明适度的跑步机 跑步可以保护小鼠免受光诱导的视网膜变性 (LIRD) 的影响，并且在 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期间和期间的视觉结果具有保护作用 通过与大脑中观察到的反应类似的生物和分子机制来衰老 锻炼身体。这将通过两个目标在简单的研究设计中进行测试： 在目标 1 中，我们将优化锻炼方案以获得最大程度的保护。幼儿（3个月大）和老年人（12- 18 个月大）的小鼠将在跑步机上以不同的持续时间、速度和间歇性跑步。视网膜 损伤（例如 LIRD）或基因损伤（例如 Tvrm4 小鼠模型）会诱发变性。 视网膜色素变性，替代 rd10 小鼠）。这些实验将指导我们运动的选择 探索神经保护机制的方案。 在目标 2 中，我们将测试运动引起的视网膜保护是否是通过对视网膜的影响来实现的。 炎症途径和能量稳态。我们的初步研究结果支持脑源性药物的作用 神经营养因子（BDNF）和抑制反应性神经胶质增生。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，我们将测试运动是否对表现出高炎症的老年小鼠具有保护作用。 对损伤和退化的反应。 锻炼既简单又便宜，而且适合很多人。它具有已知的额外好处 非视觉疾病。它应该很快转化为临床。我们的实验将改变我们的根本 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。

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.