
When the human heart struggles to maintain its rhythm due to illness or defects, electrical stimulation via a pacemaker is the standard solution. This battery-powered device is implanted under the skin, with a lead connecting directly to the heart. Despite its effectiveness, the surgical procedure can lead to painful recovery and complications like muscle soreness or infections. Researchers at Lehigh University have advanced noninvasive optogenetic cardiac pacing, using light to regulate the heartbeats of genetically altered Drosophila melanogaster, or fruit flies, a key model in research. (Humans and fruit flies share 75 percent of disease-causing genes.) Their findings, published in Science Advances, could pave the way for noninvasive heart pacing in humans.
While optogenetics is commonly used in neuroscience to manipulate neuronal activity, its application in heart pacing has only been explored since 2010. This study marks the first successful use of light to regulate the heart rhythms of fruit flies.
In this experiment, the fruit flies' DNA was altered to produce a light-sensitive protein, channelrhodopsin-2 [PDF], typically found in the eye, within their hearts. Chao Zhou, a senior study author and assistant professor of electrical engineering and bioengineering at Lehigh, explains, “When light is directed at the heart, these proteins open an ion channel, allowing a current to pass and generate an electrical signal.” This signal triggers the heart muscle to contract. By precisely timing the light pulses, the team could control the heart rates of the flies at various life stages—larva, pupa, and adult—and observe the effects. "Unlike electrical stimulation,” Zhou notes to mental_floss, “optical pacing does not harm the sample.”
A diagram of the combined optical coherence microscopy imaging and pacing setup. The fruit fly (Drosophila) is positioned at the lower right. Image credit: Alex et al. in Science Advances
Beyond using optogenetics to regulate heart rate, the team also employed a real-time imaging method called optical coherence microscopy, tailored for this study, to observe the intricate details of the flies’ hearts. This technique captures images at 130 frames per second with high axial and transverse resolution. “Flies are small, so we rely on this imaging method to visualize the heart chamber,” Zhou explains. “It’s akin to performing a miniature CT scan, powerful enough to observe the fly’s heart in action. This ensures the pacing is functioning correctly.”
Zhou and his colleagues believe this research marks the start of groundbreaking work that could eventually lead to light-based heart pacing in humans. However, significant challenges remain. For instance, Drosophila skin is much thinner and more transparent than human skin, allowing light to penetrate more easily. Additionally, a noninvasive method to deliver light-sensitive proteins to the human heart has yet to be developed, though infrared light shows potential. “Near-infrared light can penetrate up to a tenth of a centimeter into human tissue,” Zhou notes. “For example, infrared mammography systems are being developed to detect cancer in breast tissue. We could potentially engineer light-sensitive proteins in humans that respond to red photons and attach a red LED to the skin’s surface, enabling the light to reach the heart.”
Before this technology can be applied to humans, researchers must also refine methods to focus light precisely on heart tissue. “Light scatters in multiple directions when shone, which presents a technical hurdle,” Zhou states. One promising approach is gene therapy, where small DNA segments are delivered to specific body areas. “Perhaps we could encapsulate the DNA in a harmless virus, inject it into the bloodstream, and program it to accumulate in the heart,” he suggests. “Once delivered, the virus could be eliminated from the body.”
Although the research is in its early stages, Zhou highlights its potential for advancing heart-related studies. “If specific genes linked to human heart disease or congenital defects are identified, we can replicate these mutations in flies and induce similar heart conditions,” he explains. “Using light during early developmental stages, we can attempt to restore normal heart function.”
It will likely be decades before this technology reaches human hearts. Zhou estimates that light-activated cardiac pacing won’t be ready for human trials for at least 20 years.
