Computational modeling of cardiac optogenetics: Methodology overview & review of findings from simulations.
Computational modeling of cardiac optogenetics: Methodology overview & review of findings from simulations.
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DOI：
10.1016/j.compbiomed.2015.04.036
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发表时间：
2015-10-01
影响因子：
7.7
通讯作者：
Trayanova NA
中科院分区：
文献类型：
--
作者：
Boyle PM;Karathanos TV;Entcheva E;Trayanova NA
心脏光遗传学正在成为一个令人兴奋的新的潜在途径，使时空精确控制的兴奋细胞和组织在心脏中的低能量的光学刺激。这种方法涉及通过病毒基因或细胞递送在靶心脏组织中表达外源性光敏蛋白（视蛋白）。光遗传学修饰的细胞、组织和生物体的初步实验在证明基本应用的可行性方面取得了很大进展，包括使用光刺激来调节或破坏折返活动。然而，目前还不清楚基于这种有趣技术的技术是否可以扩大规模并用于人类的新临床应用，例如无痛光学除颤或动作电位形状的动态调制。回答这些问题的关键一步是探索潜在的基于光遗传学的疗法，使用复杂的计算机模拟工具，能够在生物解剖学详细的、患者特定的人类心脏模型中逼真地表示视蛋白递送和光刺激。本综述提供了（1）在现有虚拟心脏平台中代表基于光遗传学的解决方案所需的方法学发展的详细概述，以及（2）对从此类模拟中得出的结果进行调查，并对其在该领域进展方面的重要性进行严格评估。
Cardiac optogenetics is emerging as an exciting new potential avenue to enable spatiotemporally precise control of excitable cells and tissue in the heart with low-energy optical stimuli. This approach involves the expression of exogenous light-sensitive proteins (opsins) in target heart tissue via viral gene or cell delivery. Preliminary experiments in optogenetically-modified cells, tissue, and organisms have made great strides towards demonstrating the feasibility of basic applications, including the use of light stimuli to pace or disrupt reentrant activity. However, it remains unknown whether techniques based on this intriguing technology could be scaled up and used in humans for novel clinical applications, such as pain-free optical defibrillation or dynamic modulation of action potential shape. A key step towards answering such questions is to explore potential optogenetics-based therapies using sophisticated computer simulation tools capable of realistically representing opsin delivery and light stimulation in biophysically detailed, patient-specific models of the human heart. This review provides (1) a detailed overview of the methodological developments necessary to represent optogenetics-based solutions in existing virtual heart platforms and (2) a survey of findings that have been derived from such simulations and a critical assessment of their significance with respect to the progress of the field.