Three years ago, when Dan Berkowitz moved to an updated lab, he didn’t consider the potential benefits of gaining a lighting system activated by motion. Not only has it helped The Johns Hopkins Hospital’s director of cardiac anesthesia and his team see their blood vessel experiments more clearly, but it also has triggered an accidental discovery that may prove transformative in treating aneurysms and other vascular diseases.
According to Berkowitz, one day in the new lab in the Ross Research Building, lead investigator Gautam Sikka noticed that the tension in the blood vessels of mice being studied would decrease whenever the motion-activated lights came on when he entered the room. When he mentioned the finding to Berkowitz, it validated a hunch the scientist held about the phenomenon known as photorelaxation. “I had this slightly insane idea,” Berkowitz explains. “What if there were receptors for light on blood vessels? Perhaps the blood vessels had ‘eyes’ that could ‘see’ the light.”
Before long, the researchers identified a light receptor that was causing the blood vessels to relax. Next, they pinpointed the precise wavelength at which the receptor, melanopsin, was activated and at which the blood vessels showed the greatest relaxation. Then the scientists looked at how wavelength-specific light increased blood flow in the tails of normal mice but not in the tails of those that lacked the receptor, also known as opsin 4. The researchers found that the blood vessels of mice without the receptor did not relax at all in response to light.
Berkowitz says that opsin 4 is one of a group of nonimage-forming light receptors that are also found in the human retina. They help set the circadian rhythms that affect the body’s daily cycle of physical, mental and behavioral changes. Berkowitz also believes these receptors are present in blood vessels elsewhere in the human body.
“If we can develop novel ways of delivering light to blood vessels,” Berkowitz says, “this molecular switch for relaxation could be harnessed to treat all types of vascular disease.” These include peripheral artery disease, aneurysms and Raynaud’s disease, a condition causing people to feel numbness and cold in their fingers and toes due to the narrowing of the small arteries that supply blood to the skin.
He says his team hopes to develop a new treatment for Raynaud’s that directs wavelength-specific light at the blood vessels’ opsin 4 receptors.
“We plan to use high-intensity, light-emitting diodes—LEDs—incorporated into gloves as a potential mode of therapy for these patients,” says Berkowitz. (A patent on this product has been filed.) “Additionally, socks with LEDs could be used in diabetic patients to potentially enhance blood flow and heal chronic ischemic ulcers.”
Senior author of the study that was published last fall in Proceedings of the National Academy of Sciences, Berkowitz has a joint appointment in the Department of Biomedical Engineering. Trained in South Africa, the anesthesiologist has spent most of his 21-year Johns Hopkins career studying mechanisms of vascular disease.
In his clinical work, Berkowitz often sees the effects of aging, damaged vascular cells. “Critical care anesthesia often amounts to vascular system management,” he says, “so it definitely has a connection to my vascular biology research.”
Berkowitz’s research focuses on specific targets in the endothelial cells that line blood vessels. He wants to know precisely what causes endothelial cells to get injured—a state that leads to the artery-hardening plaque that precedes strokes, heart attacks and other vascular problems.