Alterations in visible light exposure modulate platelet function and regulate thrombus formation

Background: Variations in light exposure are associated with changes in inflammation and coagulation. The impact of light spectra on venous thrombosis (VT) and arterial thrombosis is largely unexplored. Objectives: To investigate the impact of altering light spectrum on platelet function in thrombosis. Methods: Wild-type C57BL/6J mice were exposed to ambient (mice^white, 400 lux), blue (mice^blue, 442 nm, 1400 lux), or red light (mice^red, 617 nm, 1400 lux) with 12:12 hour light:dark cycle for 72 hours. After 72 hours of light exposure, platelet aggregation, activation, transcriptomic, and metabolomic changes were measured. The ability of released products of platelet activation to induce thrombosis-generating neutrophil extracellular trap formation was quantified. Subsequent thrombosis was measured using murine models of VT and stroke. To translate our findings to human patients, light-filtering cataract patients were evaluated over an 8-year period for rate of venous thromboembolism with multivariable logistic regression clustered by hospital. Results: Exposure to long-wavelength red light resulted in reduced platelet aggregation and activation. RNA-seq analysis demonstrated no significant transcriptomic changes between mice^red and mice^white. However, there were global metabolomic changes in platelets from mice^red compared with mice^white. Releasate from activated platelets resulted in reduced neutrophil extracellular trap formation. Mice^red also had reduced VT weight and brain infarct size following stroke. On subgroup analysis of cataract patients, patients with a history of cancer had a lower lifetime risk of venous thromboembolism after implantation with lenses that filter low-wavelength light. Conclusion: Light therapy may be a promising approach to thrombus prophylaxis by specifically targeting the intersection between innate immune function and coagulation.