Humans and mice exposed to long-wavelength red light had lower rates of blood clots that can cause heart attacks, lung damage and strokes, according to research led by University of Pittsburgh School of Medicine and UPMC surgeon-scientists and published today in the Journal of Thrombosis and Haemostasis.
The findings, which need to be verified through clinical trials, have the potential to reduce blood clots in veins and arteries, which are leading causes of preventable death worldwide.
"The light we're exposed to can change our biological processes and change our health," said lead author Elizabeth Andraska, M.D., assistant professor of surgery in Pitt's Trauma and Transfusion Medicine Research Center and vascular surgery resident at UPMC. "Our findings could lead to a relatively inexpensive therapy that would benefit millions of people."
Scientists have long connected light exposure to health outcomes. The rising and setting of the sun underlies metabolism, hormone secretion, even the flow of blood, and heart attacks and stroke are more likely to happen in the morning hours than at night. Andraska and her colleagues wondered if light could have an impact on the blood clots that lead to these conditions.
To test this idea, the team exposed mice to 12 hours of either red, blue or white light, followed by 12 hours of darkness, in a 72-hour cycle. They then looked for differences in blood clots between the groups. The mice exposed to red light had nearly five times fewer clots than the mice exposed to blue or white light. Activity, sleep, eating, weight and body temperature remained the same between the groups.
The team also analyzed existing data on more than 10,000 patients who had cataract surgery and received either conventional lenses that transmit the entire visible spectrum of light, or blue light-filtering lenses, which transmit about 50% less blue light. They discovered that cancer patients who received blue light-filtering lenses had lower risk of blood clots compared to their counterparts with conventional lenses. This is especially notable because cancer patients have nine times the risk of blood clots of non-cancer patients.
"These results are unraveling a fascinating mystery about how the light to which we're exposed on a daily basis influences our body's response to injury," said senior author Matthew Neal, M.D., professor of surgery, Watson Fund in Surgery Chair and co-director of the Trauma and Transfusion Medicine Research Center at Pitt, and trauma surgeon at UPMC. "Our next steps are to figure out why, biologically, this is happening, and to test if exposing people at high risk for blood clots to more red light lowers that risk. Getting to the bottom of our discovery has the potential to massively reduce the number of deaths and disabilities caused by blood clots worldwide."
The recently published study indicates that the optic pathway is key – light wavelength didn't have any impact on blind mice, and shining light directly on blood also didn't cause a change in clotting.
The team observed that red light exposure is associated with less inflammation and activation of the immune system. For example, red light-exposed mice had fewer neutrophil extracellular traps – aptly abbreviated as "NETs" – which are web-like structures made by immune cells to trap invading microorganisms. They also trap platelets, which can lead to clots.
The mice exposed to red light also had increased fatty acid production, which reduces platelet activation. Since platelets are essential to forming clots, this naturally leads to less clot formation.
Understanding how the red light is triggering changes that lower clotting risk could also put scientists on the track of better medications or therapies that could be more potent and convenient for patients than continuous red light exposure.
In preparation for clinical trials, the team is developing red light goggles to control the amount of light exposure study participants receive and investigating who may most benefit from red light
Additional authors on this research are Frederik Denorme, Ph.D., Robert Campbell, Ph.D., and Matthew R. Rosengart, M.D., all of Washington University in St. Louis; Christof Kaltenmeier, M.D., Aishwarrya Arivudainabi, Emily P. Mihalko, Ph.D., Mitchell Dyer, M.D., Gowtham K. Annarapu, Ph.D., Mohammadreza Zarisfi, M.D., Patricia Loughran, Ph.D., Mehves Ozel, M.D., Kelly Williamson, Ph.D., Roberto Mota-Alvidrez, M.D., Sruti Shiva, Ph.D., Susan Shea, Ph.D., and Richard A. Steinman, M.D., Ph.D., all of Pitt; and Kimberly Thomas, Ph.D., of Vitalant Research Institute.
This research was supported by National Institutes of Health grants R35GM119526, K01AG059892, R01HL163019, R01GM147121, R01GM145674, T32HL98036 and S10OD028483, the University of Pittsburgh Center for Research Computing, National Center for Research Resources Shared Instrumentation grants 1S10OD016232-01, 1S10OD018210-01A1 and 1S10OD021505-01, American Heart Association 2021Post830138 award, and a Physician-Scientist Institutional Award from the Burroughs Wellcome Fund.
