Optogenetics: The Promise for development of Biological Alternatives to the Electronic Pacemaker: Pacing and Resynchronizing Heartbeat by Activating Light-sensitive Proteins: ion-channel ChR2, overexpressed in Excitable cells in Heart Muscle Cells to modulate their Electrical Activity
Reporter: Aviva Lev-Ari, PhD, RN
Optogenetics for in vivo cardiac pacing and resynchronization therapies
- Nature Biotechnology 33, 750–754 (2015) doi:10.1038/nbt.3268
- Received
- 28 February 2014
- Accepted
- 22 May 2015
- Published online
- 22 June 2015
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.
The study was conducted by Dr. Udi Nussinovitch as part of his PhD work in Professor Gepstein’s laboratory at the Technion. Dr. Nussinovitch is currently an intern at the Department of Internal Medicine at Rambam.
The optogenetic technology employed allowed researchers to selectively activate light-sensitive proteins (such as the ion-channel ChR2, first identified in algae), which were overexpressed in excitable cells (such as nerve or muscle cells), in an attempt to modulate (either augment or suppress) their electrical activity. Optogenetics has become an important tool in brain research and the current study is the first to translate this important innovation to pace and resynchronize the heartbeat.
In the study, conducted in rats, the researchers first directed a beam of blue light at an area in the heart where the light-sensitive genes were delivered. This resulted in effective pacing of the heart at different rates as dictated by the frequency of the blue light flashes applied. Subsequently, a more advanced experiment was conducted, in which various locations in the rat hearts expressing ChR2 were activated simultaneously by light, resulting in improved synchronization of the contractions of the ventricles.
Professor Gepstein stresses that this is a preliminary study, and that “in order to translate the aforementioned approach to the clinical arena, we must overcome some significant hurdles. We must
- improve the penetration of light through the tissues,
- ensure continuous expression of the protein in the heart for many years, and
- develop a unique pacing device that will provide the necessary illumination.
But despite all of this, the results of the study demonstrate the unique potential of optogenetics for both
- cardiac pacing (as an alternative to electronic pacemakers) and
- resynchronization (for the treatment of heart failure with ventricular dys-synchrony) therapies.”
SOURCES
Nature Biotechnology 33, 750–754 (2015) doi:10.1038/nbt.3268
http://pard.technion.ac.il/2015/06/22/the-illuminated-heart/
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