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心脏光遗传学:一种治疗心血管疾病的新方法。

Cardiac optogenetics: a novel approach to cardiovascular disease therapy.

机构信息

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, PR China.

Cardiovascular Research Institute, Wuhan University, Wuhan, PR China.

出版信息

Europace. 2018 Nov 1;20(11):1741-1749. doi: 10.1093/europace/eux345.

Abstract

Optogenetics is a cell-type specific and high spatial-temporal resolution method that combines genetic encoding of light-sensitive proteins and optical manipulation techniques. Optogenetics technology provides a novel approach for research on cardiac arrhythmia treatment, including pacing, recovering the conduction system, and achieving cardiac resynchronization with precise and low-energy optical control. Photosensitive proteins, which usually act as ion channels, pumps, or receptors, are delivered to target cells, where they respond to light pulses of specific wavelengths, evoke transient flows of transmembrane ion currents, and induce signal transmission. With the development of gene technology, the in vivo efficiency of optogenetics in cardiology has been trialed, and in vitro experiments have been performed to test its potential in cardiac electrophysiology. Challenges for applying optogenetics in large animals and humans include the effectiveness, safety, and long-term expression of photosensitive proteins, unscattered and unattenuated exogenous light stimulation, and the need for implantable miniature light stimulators. Photosensitive proteins, genetic engineering technology, and light equipment are essential for experiments in cardiac optogenetics. Optogenetics may provide an alternative method for evaluating the mechanism of cardiac arrhythmias, testing hypotheses, and treating cardiovascular diseases.

摘要

光遗传学是一种细胞类型特异性和高时空分辨率的方法,它结合了光敏感蛋白的遗传编码和光学操纵技术。光遗传学技术为心律失常治疗的研究提供了一种新方法,包括起搏、恢复传导系统以及通过精确和低能量的光学控制实现心脏再同步。光敏蛋白通常作为离子通道、泵或受体起作用,被递送到靶细胞,在那里它们响应特定波长的光脉冲,引起跨膜离子电流的短暂流动,并诱导信号传递。随着基因技术的发展,光遗传学在心脏病学中的体内效率已经进行了试验,并且已经进行了体外实验来测试其在心脏电生理学中的潜力。将光遗传学应用于大动物和人类的挑战包括光敏蛋白的有效性、安全性和长期表达、外源性光刺激的无散射和无衰减,以及对可植入微型光刺激器的需求。光敏蛋白、基因工程技术和光设备是心脏光遗传学实验的必要条件。光遗传学可能为评估心律失常机制、检验假说和治疗心血管疾病提供一种替代方法。

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