Light Exposure Alters Platelet-mediated Thrombosis

Description of Background: The risk of thrombotic events such as venous thrombosis (VT) and stroke have been found to oscillate with the day-light cycle. The aim of this study was to investigate the impact of altering light exposure on platelet function in thrombosis.

Methods: WT C57BL/6J mice were exposed to ambient (micewhite, 300lux) or long wavelength red light (micered, 617nm, 1,700lux). After 72 hours of light exposure, platelet aggregation and activation were measured. Platelets were isolated and evaluated for transcriptomic and metabolomic changes. The ability of released products of platelet activation to induce thrombosis-generating NET formation was quantified. Subsequent thrombosis was measured using a murine models of VT and stroke. Hemostasis was measured with tail bleeding assays and coagulation biomarkers. We compared patients undergoing cataract surgery with implantation of low-wavelength filtering intraocular lenses (IOL) versus natural IOL over 8-years for risk of VT using multivariable logistic regression clustered by hospital.

Results: Exposure to long wavelength red light resulted in reduced platelet aggregation (micered 16.0±4.1 vs. micewhite 23.8±5.6 Ohm, p=.02) and activation (P-selectin; micered 35.2% vs. micewhite 53.2%; p=.02; Figure 1). Hemostasis assays were not significantly different between groups when mice were exposed to different wavelengths of light. RNA-seq analysis demonstrated no significant transcriptomic changes between micered and micewhite. There were global metabolomic changes in platelets from micered compared to micewhite. Releasate from activated platelets resulted in reduced NET formation (fold increase from control: micered 1.1 vs. micewhite 1.9, p=.03). Micered had reduced VT weight (micered 4.2±5.1 mg vs. micewhite 16.5±7.7 mg; p<.01) and brain infarct size following stroke (micered 38.8±17.6 mm3 vs. micewhite 73.3±15.0 mm3; p<.01). In a risk adjusted analysis, low-wavelength filtering IOL were associated with a reduced risk of VTE (OR 0.89; 95% CI 0.80-0.99; p=.04).

Conclusion: Exposure to long wavelength red light results in reduced platelet aggregation and activation. Light exposure modulation is a promising alternative for prophylaxis of venous and arterial thrombosis.

Learning Objective: Light exposure effects platelet mediated thrombosis.