Chu-Tan Joshua A, Cioanca Adrian V, Wooff Yvette, Kirkby Max, Ellis Marissa, Gulati Pranay, Karl Tim, Boatright Jeffrey H, Bales Katie, Nickerson John, Natoli Riccardo
Eccles Institute of Neuroscience, John Curtin School of Medical Research, College of Health and Medicine, The Australian National University, Acton, ACT, Australia.
School of Medicine and Psychology, College of Health and Medicine, The Australian National University, Acton, ACT, Australia.
Front Physiol. 2023 Mar 10;14:1116898. doi: 10.3389/fphys.2023.1116898. eCollection 2023.
Exercise has been shown to promote a healthier and longer life and linked to a reduced risk of developing neurodegenerative diseases including retinal degenerations. However, the molecular pathways underpinning exercise-induced cellular protection are not well understood. In this work we aim to profile the molecular changes underlying exercise-induced retinal protection and investigate how exercise-induced inflammatory pathway modulation may slow the progression of retinal degenerations. Female C57Bl/6J mice at 6 weeks old were given free access to open voluntary running wheels for a period of 28 days and then subjected to 5 days of photo-oxidative damage (PD)-induced retinal degeneration. Following, retinal function (electroretinography; ERG), morphology (optical coherence tomography; OCT) and measures of cell death (TUNEL) and inflammation (IBA1) were analysed and compared to sedentary controls. To decipher global gene expression changes as a result of voluntary exercise, RNA sequencing and pathway and modular gene co-expression analyses were performed on retinal lysates of exercised and sedentary mice that were subjected to PD, as well as healthy dim-reared controls. Following 5 days of PD, exercised mice had significantly preserved retinal function, integrity and reduced levels of retinal cell death and inflammation, compared to sedentary controls. In response to voluntary exercise, inflammatory and extracellular matrix integrity pathways were significantly modulated, with the gene expression profile of exercised mice more closely trending towards that of a healthy dim-reared retina. We suggest that voluntary exercise may mediate retinal protection by influencing key pathways involved in regulating retinal health and shifting the transcriptomic profile to a healthy phenotype.
运动已被证明能促进更健康、更长寿的生活，并与降低包括视网膜退化在内的神经退行性疾病的发病风险有关。然而，运动诱导细胞保护的分子途径尚未得到充分理解。在这项研究中，我们旨在描绘运动诱导视网膜保护的分子变化，并研究运动诱导的炎症途径调节如何减缓视网膜退化的进程。6周龄的雌性C57Bl/6J小鼠可自由使用开放式自愿跑步轮28天，然后接受5天的光氧化损伤（PD）诱导的视网膜退化。随后，分析视网膜功能（视网膜电图；ERG）、形态（光学相干断层扫描；OCT）以及细胞死亡（TUNEL）和炎症（IBA1）的指标，并与久坐不动的对照组进行比较。为了解析自愿运动导致的全球基因表达变化，对接受PD处理的运动小鼠和久坐不动小鼠以及健康的暗光饲养对照小鼠的视网膜裂解物进行了RNA测序以及通路和模块基因共表达分析。在PD处理5天后，与久坐不动的对照组相比，运动小鼠的视网膜功能、完整性得到显著保留，视网膜细胞死亡和炎症水平降低。作为对自愿运动的反应，炎症和细胞外基质完整性通路受到显著调节，运动小鼠的基因表达谱更接近健康的暗光饲养视网膜。我们认为，自愿运动可能通过影响参与调节视网膜健康的关键途径并将转录组谱转变为健康表型来介导视网膜保护。
