Boyle Patrick M, Karathanos Thomas V, Trayanova Natalia A
Institute for Computational Medicine, Johns Hopkins University, 316 Hackerman Hall, 3400 N Charles Street, Baltimore, MD 21218; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD.
Institute for Computational Medicine, Johns Hopkins University, 316 Hackerman Hall, 3400 N Charles Street, Baltimore, MD 21218; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD.
Trends Cardiovasc Med. 2015 Feb;25(2):73-81. doi: 10.1016/j.tcm.2014.10.004. Epub 2014 Oct 16.
Optogenetics is an exciting new technology in which viral gene or cell delivery is used to inscribe light sensitivity in excitable tissue to enable optical control of bioelectric behavior. Initial progress in the fledgling domain of cardiac optogenetics has included in vitro expression of various light-sensitive proteins in cell monolayers and transgenic animals to demonstrate an array of potentially useful applications, including light-based pacing, silencing of spontaneous activity, and spiral wave termination. In parallel to these developments, the cardiac modeling community has developed a versatile computational framework capable of realistically simulating optogenetics in biophysically detailed, patient-specific representations of the human heart, enabling the exploration of potential clinical applications in a predictive virtual platform. Toward the ultimate goal of assessing the feasibility and potential impact of optogenetics-based therapies in cardiovascular medicine, this review provides (1) a detailed synopsis of in vivo, in vitro, and in silico developments in the field and (2) a critical assessment of how existing clinical technology for gene/cell delivery and intra-cardiac illumination could be harnessed to achieve such lofty goals as light-based arrhythmia termination.
光遗传学是一项令人兴奋的新技术,其中病毒基因或细胞递送被用于在可兴奋组织中赋予光敏感性,从而实现对生物电行为的光学控制。心脏光遗传学这一新兴领域的初步进展包括在细胞单层和转基因动物中体外表达各种光敏感蛋白,以展示一系列潜在的有用应用,包括基于光的起搏、自发活动的沉默和螺旋波终止。与这些进展同时,心脏建模界已经开发出一个通用的计算框架,能够在生物物理细节丰富、针对患者的人体心脏模型中逼真地模拟光遗传学,从而在一个预测性虚拟平台上探索潜在的临床应用。为了评估基于光遗传学的疗法在心血管医学中的可行性和潜在影响这一最终目标,本综述提供了:(1)该领域体内、体外和计算机模拟方面进展的详细概述;(2)对如何利用现有的基因/细胞递送和心内照明临床技术来实现诸如基于光的心律失常终止等崇高目标的批判性评估。