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Optogenetics for in vivo cardiac pacing and resynchronization therapies

Nature Biotechnology volume 33, pages 750–754 (2015)Cite this article

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Abstract

Abnormalities in the specialized cardiac conduction system may result in slow heart rate or mechanical dyssynchrony. Here we apply optogenetics, widely used to modulate neuronal excitability1,2,3,4, for cardiac pacing and resynchronization. We used adeno-associated virus (AAV) 9 to express the Channelrhodopsin-2 (ChR2) transgene at one or more ventricular sites in rats. This allowed optogenetic pacing of the hearts at different beating frequencies with blue-light illumination both in vivo and in isolated perfused hearts. Optical mapping confirmed that the source of the new pacemaker activity was the site of ChR2 transgene delivery. Notably, diffuse illumination of hearts where the ChR2 transgene was delivered to several ventricular sites resulted in electrical synchronization and significant shortening of ventricular activation times. These findings highlight the unique potential of optogenetics for cardiac pacing and resynchronization therapies.

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Figure 1: Optogenetic pacing of the rat heart in vivo.
Figure 2: Optogenetic pacing in the isolated rat heart.
Figure 3: Dual-site and multisite optogenetic pacing in the isolated rat heart setting.

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Acknowledgements

This study was supported in part by the NOFAR project from the Office of the Chief Scientist (OCS) in the Israel Ministry of Economy, by the Israel Science Foundation (1609/14) and by the Nancy & Stephen Grand Philanthropic Fund. We thank C. Giridish for his technical help with the light sources. Also, we wish to thank I. Huber (from the Rappaport Faculty of Medicine, Technion), E. Suss-Toby, M. Holdengreber Shahar and L. Leiba (Imaging center at the Faculty of Medicine, Technion) and S. Ben Eliezer (Pathology Department, Rambam Health Center, Haifa, Israel) for their help with histological slide processing and their assistance with results analysis.

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Authors and Affiliations

  1. The Sohnis Laboratory for Cardiac Electrophysiology and Regenerative Medicine, Rappaport Faculty of Medicine and Research Institute, Technion-Institute of Technology, Haifa, Israel

    Udi Nussinovitch & Lior Gepstein

  2. Rambam Health Care Campus, Haifa, Israel

    Udi Nussinovitch & Lior Gepstein

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  1. Udi Nussinovitch
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  2. Lior Gepstein
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Contributions

U.N. and L.G. designed the experiments, U.N. performed the experiments and analyzed the results, U.N. and L.G. wrote the manuscript. All authors read and approved the manuscript.

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Correspondence to Lior Gepstein.

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The authors declare no competing financial interests.

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Nussinovitch, U., Gepstein, L. Optogenetics for in vivo cardiac pacing and resynchronization therapies. Nat Biotechnol 33, 750–754 (2015). https://doi.org/10.1038/nbt.3268

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