When it comes to the fast pace of biotechnology, missing a beat is never good. Building on that principle, a talented team from Israel used optogenetics to resynchronize hearts with just that problem.
Optogenetic systems are showing tremendous clinical potential, whether it be bringing eyesight to the blind or restoring excitable physiology, they offer a biological workaround for current surgical and pharmaceutical therapeutics.
In its latest miracle, optogenetics was applied to the heart to help synchronize some struggling ventricles, helping them get all their cells on the same page.
Here’s what went down:
- Adeno-associated virus (AAV) 9 delivered the excitable Channelrhodopsin-2 (ChR2) to the ventricles of rats.
- ChR2 enabled optogenetic pacing of the heart in vivo, at a number of different beating frequencies that depended on the rate of blue light flashes per minute coming from the 2mm fiber-coupled monochromic LED.
- Using optical mapping, it was confirmed that pacemaker activity was coming from the site of transfection and not its usual location.
- In isolated perfused hearts, delivering the transgene to many different sites produced a synergy of electrical synchronization and resulted in quicker ventricular activation.
Ultimately, not only does the work show the clinical potential of an optogenetic pacemaker, but it also highlights some incredible adaptability in the mammalian heart.
Senior author Lior Gepstien shares that “Our work is the first to suggest a non-electrical approach to cardiac resynchronization therapy. Before this, there have been a number of elegant gene therapy and cell therapy approaches for generating biological pacemakers that can pace the heart from a single spot. However, it was impossible to use such approaches to activate the heart simultaneously from a number of sites for resynchronization therapy.”
The Optogenetic ‘Doppler Effect’: Shifting from Blue to Red
When it comes to the physical limitations of blue light, tissue penetration becomes a problem in larger animals, like us humans. Gepstien concludes, “This means that the affected cells have to be relatively superficial, near the surface of the heart, and that an optical fiber should be implanted, bringing the illumination beam as close as possible to the cells. A potential solution in the future may be the development of similar light-sensitive proteins that will be responsive to light in the near-red or even infra-red spectrum, which penetrates tissue much better, allowing illumination from a long distance.”
Keep up with the pace at Nature Biotechnology, June 2015