Alex Aneesh, Li Airong, Tanzi Rudolph E, Zhou Chao
Department of Electrical and Computer Engineering, Lehigh University, Bethlehem, PA 18015, USA. ; Center for Photonics and Nanoelectronics, Lehigh University, Bethlehem, PA 18015, USA.
Genetics and Aging Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
Sci Adv. 2015 Oct 9;1(9):e1500639. doi: 10.1126/sciadv.1500639. eCollection 2015 Oct.
Electrical stimulation is currently the gold standard for cardiac pacing. However, it is invasive and nonspecific for cardiac tissues. We recently developed a noninvasive cardiac pacing technique using optogenetic tools, which are widely used in neuroscience. Optogenetic pacing of the heart provides high spatial and temporal precisions, is specific for cardiac tissues, avoids artifacts associated with electrical stimulation, and therefore promises to be a powerful tool in basic cardiac research. We demonstrated optogenetic control of heart rhythm in a well-established model organism, Drosophila melanogaster. We developed transgenic flies expressing a light-gated cation channel, channelrhodopsin-2 (ChR2), specifically in their hearts and demonstrated successful optogenetic pacing of ChR2-expressing Drosophila at different developmental stages, including the larva, pupa, and adult stages. A high-speed and ultrahigh-resolution optical coherence microscopy imaging system that is capable of providing images at a rate of 130 frames/s with axial and transverse resolutions of 1.5 and 3.9 μm, respectively, was used to noninvasively monitor Drosophila cardiac function and its response to pacing stimulation. The development of a noninvasive integrated optical pacing and imaging system provides a novel platform for performing research studies in developmental cardiology.
电刺激是目前心脏起搏的金标准。然而，它具有侵入性且对心脏组织缺乏特异性。我们最近利用光遗传学工具开发了一种非侵入性心脏起搏技术，该工具在神经科学中广泛应用。心脏的光遗传学起搏具有高空间和时间精度，对心脏组织具有特异性，避免了与电刺激相关的伪迹，因此有望成为基础心脏研究中的有力工具。我们在一种成熟的模式生物黑腹果蝇中展示了心律的光遗传学控制。我们开发了在心脏中特异性表达光门控阳离子通道——视紫红质-2（ChR2）的转基因果蝇，并证明了在包括幼虫、蛹和成虫阶段在内的不同发育阶段，对表达ChR2的果蝇成功进行了光遗传学起搏。一种能够以130帧/秒的速率提供图像，轴向分辨率为1.5μm、横向分辨率为3.9μm的高速和超高分辨率光学相干显微镜成像系统，被用于非侵入性监测果蝇心脏功能及其对起搏刺激的反应。非侵入性集成光学起搏和成像系统的开发为开展发育心脏病学研究提供了一个新平台。
