Joshi Jyotsna, Rubart Michael, Zhu Wuqiang
Department of Cardiovascular Medicine, Physiology and Biomedical Engineering, Mayo Clinic, Phoenix, AZ, United States.
Department of Pediatrics, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, United States.
Front Bioeng Biotechnol. 2020 Jan 29;7:466. doi: 10.3389/fbioe.2019.00466. eCollection 2019.
Optogenetics is an elegant approach of precisely controlling and monitoring the biological functions of a cell, group of cells, tissues, or organs with high temporal and spatial resolution by using optical system and genetic engineering technologies. The field evolved with the need to precisely control neurons and decipher neural circuity and has made great accomplishments in neuroscience. It also evolved in cardiovascular research almost a decade ago and has made considerable progress in both and animal studies. Thus, this review is written with an objective to provide information on the evolution, background, methodical advances, and potential scope of the field for cardiovascular research and medicine. We begin with a review of literatures on optogenetic proteins related to their origin, structure, types, mechanism of action, methods to improve their performance, and the delivery vehicles and methods to express such proteins on target cells and tissues for cardiovascular research. Next, we reviewed historical and recent literatures to demonstrate the scope of optogenetics for cardiovascular research and regenerative medicine and examined that cardiac optogenetics is vital in mimicking heart diseases, understanding the mechanisms of disease progression and also in introducing novel therapies to treat cardiac abnormalities, such as arrhythmias. We also reviewed optogenetics as promising tools in providing high-throughput data for cardiotoxicity screening in drug development and also in deciphering dynamic roles of signaling moieties in cell signaling. Finally, we put forth considerations on the need of scaling up of the optogenetic system, clinically relevant and models, light attenuation issues, and concerns over the level, immune reactions, toxicity, and ectopic expression with opsin expression. Detailed investigations on such considerations would accelerate the translation of cardiac optogenetics from present and animal studies to clinical therapies.
光遗传学是一种通过使用光学系统和基因工程技术，以高时空分辨率精确控制和监测细胞、细胞群、组织或器官生物学功能的精妙方法。该领域随着精确控制神经元和破译神经回路的需求而发展，并在神经科学领域取得了巨大成就。大约十年前，它也在心血管研究中得到发展，在体外和动物研究中都取得了显著进展。因此，撰写本综述的目的是提供有关该领域在心血管研究和医学方面的发展、背景、方法进展以及潜在范围的信息。我们首先回顾与光遗传蛋白相关的文献，包括它们的起源、结构、类型、作用机制、提高其性能的方法，以及在心血管研究中用于在靶细胞和组织上表达此类蛋白的递送载体和方法。接下来，我们回顾了历史和近期的文献，以展示光遗传学在心血管研究和再生医学中的应用范围，并研究了心脏光遗传学在模拟心脏病、理解疾病进展机制以及引入治疗心脏异常（如心律失常）的新疗法方面的重要性。我们还回顾了光遗传学作为一种有前景的工具，在药物开发中提供高通量心脏毒性筛选数据以及破译细胞信号传导中信号分子的动态作用方面的应用。最后，我们提出了关于扩大光遗传系统规模、临床相关体外和体内模型、光衰减问题以及对视蛋白表达水平、免疫反应、毒性和异位表达的担忧等方面的考虑。对这些考虑因素的详细研究将加速心脏光遗传学从目前的体外和动物研究向临床治疗的转化。
