Department of Bioengineering, Lehigh University, Bethlehem, PA, 18015, USA.
Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, 63105, USA.
Commun Biol. 2020 Jun 29;3(1):336. doi: 10.1038/s42003-020-1065-3.
Drosophila is a powerful genetic model system for cardiovascular studies. Recently, optogenetic pacing tools have been developed to control Drosophila heart rhythm noninvasively with blue light, which has a limited penetration depth. Here we developed both a red-light sensitive opsin expressing Drosophila system and an integrated red-light stimulation and optical coherence microscopy (OCM) imaging system. We demonstrated noninvasive control of Drosophila cardiac rhythms using a single light source, including simulated tachycardia in ReaChR-expressing flies and bradycardia and cardiac arrest in halorhodopsin (NpHR)-expressing flies at multiple developmental stages. By using red excitation light, we were able to pace flies at higher efficiency and with lower power than with equivalent blue light excitation systems. The recovery dynamics after red-light stimulation of NpHR flies were observed and quantified. The combination of red-light stimulation, OCM imaging, and transgenic Drosophila systems provides a promising and easily manipulated research platform for noninvasive cardiac optogenetic studies.
果蝇是心血管研究的强大遗传模式生物系统。最近,光遗传学起搏工具已经被开发出来,可以用蓝光非侵入性地控制果蝇的心律,但其穿透深度有限。在这里,我们开发了一个对红光敏感的表达果蝇系统和一个集成的红光刺激和光学相干显微镜(OCM)成像系统。我们使用单个光源演示了对果蝇心脏节律的非侵入性控制,包括在 ReaChR 表达的果蝇中模拟心动过速,以及在多个发育阶段的 halorhodopsin(NpHR)表达的果蝇中模拟心动过缓和心脏骤停。通过使用红光激发,我们能够以比等效的蓝光激发系统更高的效率和更低的功率起搏果蝇。还观察和量化了 NpHR 果蝇在红光刺激后的恢复动力学。红光刺激、OCM 成像和转基因果蝇系统的结合为非侵入性心脏光遗传学研究提供了一个有前途且易于操作的研究平台。