When a human heart has difficulty regulating its own rhythm or “pacing,” due to illness or heart defect, electrical stimulation is the go-to treatment, in the form of a pacemaker. This small, battery-operated device is installed under the skin, with an electrical lead that connects directly to the heart. While pacemakers are highly effective, installing them requires surgery, which can occasionally come with a painful recovery and side effects like sore muscles or infection. Now, researchers at Lehigh University have made headway in noninvasive optogenetic cardiac pacing—using light pulses to regulate the heartbeats of genetically modified Drosophila melanogaster, or fruit flies, a well-established animal model. (Humans and fruit flies share 75 percent of the genes that cause disease in humans.) Their research, published recently in Science Advances, may one day lead to a noninvasive method for pacing the human heart.
Although widely used in neuroscience to control neuronal function, optogenetic heart pacing has only been clinically attempted since 2010. This was the first time researchers were able to use it to pace the heart rhythms of fruit flies.
In this study, the flies’ DNA was modified to express a light-sensitive protein typically found in the eye, channelrhodopsin-2 protein [PDF], in their hearts. According to Chao Zhou, a senior author of the study and assistant professor of electrical engineering and bioengineering at Lehigh, “When you shine light on the heart, these proteins will open an ion channel and a kind of current will pass though that generates an electrical signal.” That electrical signal causes a contraction of the heart muscle. By focusing and targeting the light at intervals, they could control the pace of the flies’ hearts at different stages of their development, including larva, pupa, and adult, and then monitor them. "Unlike electrical stimulation,” Zhou tells mental_floss, “optical pacing will not cause any harm to the sample.”
A schematic of the integrated optical coherence microscopy imaging and pacing system. The fruit fly (Drosophila) is at lower right. Image credit: Alex et al. in Science Advances
In addition to the use of optogenetics to pace heart rate, they were also able to monitor the microscopic details of the flies’ hearts using a real-time imaging technique called optical coherence microscopy, specifically designed for the experiment, that is capable of providing images at a rate of 130 frames per second with axial and transverse resolutions. “Flies are tiny, so we use this optical imaging method to see the heart chamber,” Zhou says. “It’s like we’re taking a tiny CT scan, strong enough to see a fly heart pumping. This allowed us to confirm that the pacing is working properly.”
Zhou and his team feel that this is the beginning of important research that may one day lead to light-activated cardiac pacing in humans, too. Of course, that’s a long way off. For starters, Drosophila skin is far thinner and more transparent than human skin, making it easier for the light to penetrate. Second, they have not yet found a noninvasive method to deliver light-sensitive photons to the human heart, though infrared light holds promise. “We know that near-infrared light can penetrate a tenth of a centimeter into human tissues,” Zhou says. “People are developing infrared mammography systems to see through breast tissue for any cancer, for instance. Potentially we could develop light-sensitive proteins in humans that are sensitive to these red photons, and attach a red LED to the skin surface. Then maybe they would be powerful enough to reach the heart.”
Before the technology can be applied to a human heart, they also need to create a refined way to focus the light to target only the heart tissue. “When you shine the light, it scatters in many directions, so that is another technical challenge,” Zhou says. One potential method that many researchers are focusing on, he says, is gene therapy, figuring out ways to deliver small pieces of DNA to specific places in the body. “Maybe you could pack the small DNA coding into some benign virus and inject it into the blood stream and engineer it to accumulate it in the heart," he speculates. "After you deliver it to the heart, the virus could be cleared out.”
While the research has a long way to go, Zhou says it makes other areas of study of the heart possible. “If you have certain genes that affect human heart disease, or when children are born with congenital heart defects, we can put these same gene mutations in flies and modify flies to have the same heart defects," he says. "Then we can use light in the early stages of development to try to normalize the heart.”
Don't count on this technology coming to a heart near you anytime soon. Zhou projects it will be at least 20 years before light-activated cardiac pacing will be available for human trials.