Department of Biomedical Engineering and the Institute for Computational Medicine, Johns Hopkins University, Baltimore, Maryland.
Department of Biomedical Engineering and the Institute for Computational Medicine, Johns Hopkins University, Baltimore, Maryland.
JACC Clin Electrophysiol. 2018 Feb;4(2):155-167. doi: 10.1016/j.jacep.2017.12.006. Epub 2018 Feb 1.
Cardiac optogenetics is an emergent research area involving the delivery of light-sensitive proteins (opsins) to excitable heart tissue to enable optical modulation of cardiac electrical function. Optogenetic stimulation has many noteworthy advantages over conventional electrical methods, including selective electrophysiological modulation in specifically targeted cell subpopulations, high-resolution spatiotemporal control via patterned illumination, and use of different opsins to elicit inward or outward transmembrane current. This review summarizes developments achieved since the inception of cardiac optogenetics research, which has spanned nearly a decade. The authors first provide an overview of recent methodological advances in opsin engineering, light sensitization of cardiac tissue, strategies for illuminating the heart, and frameworks for simulating optogenetics in realistic computational models of patient hearts. They then review recent cardiac optogenetics applications, including: 1) all-optical, high-throughput, contactless assays for quantification of electrophysiological properties; 2) optogenetic perturbation of cardiac tissue to unveil mechanistic insights on the initiation, perpetuation, and termination of arrhythmia; and 3) disruptive translational innovations such as light-based pacemaking and defibrillation.
心脏光遗传学是一个新兴的研究领域，涉及将光敏感蛋白（opsins）递送到可兴奋的心脏组织中，以实现心脏电功能的光学调节。光遗传学刺激相对于传统的电方法具有许多显著的优势，包括在特定靶向细胞亚群中选择性的电生理学调节、通过图案照明实现高分辨率的时空控制，以及使用不同的 opsins 来引起内向或外向跨膜电流。本综述总结了自心脏光遗传学研究开始近十年以来所取得的进展。作者首先概述了 opsin 工程、心脏组织的光敏化、照明策略以及在患者心脏的真实计算模型中模拟光遗传学的框架方面的最新方法学进展。然后，他们回顾了最近的心脏光遗传学应用，包括：1）用于量化电生理特性的全光学、高通量、非接触式检测；2）光遗传学对心脏组织的扰动，以揭示心律失常的起始、持续和终止的机制见解；以及 3）光起搏和除颤等颠覆性的转化创新。
