A train of blue light pulses delivered through closed eyelids suppresses melatonin and phase shifts the human circadian system

Abstract

A model of circadian phototransduction was published in 2005 to predict the spectral sensitivity of the human circadian system to narrow-band and polychromatic light sources by combining responses to light from the spectral-opponent “blue” versus “yellow” cone bipolar pathway with direct responses to light by the intrinsically photosensitive retinal ganglion cells. In the model, depolarizing “blue” responses, but not hyperpolarizing “yellow” responses, from the “blue” versus “yellow” pathway are combined with the intrinsically photosensitive retinal ganglion cell responses. Intrinsically photosensitive retinal ganglion cell neurons are known to be much slower to respond to light than the cone pathway, so an implication of the model is that periodic flashes of “blue” light, but not “yellow” light, would be effective for stimulating the circadian system. A within-subjects study was designed to test the implications of the model regarding retinal exposures to brief flashes of light. The study was also aimed at broadening the foundation for clinical treatment of circadian sleep disorders by delivering flashing light through closed eyelids while people were asleep. In addition to a dark control night, the eyelids of 16 subjects were exposed to three light-stimulus conditions in the phase delay portion of the phase response curve while they were asleep: (1) 2-second flashes of 111 W/m² of blue (λ_max ≈ 480 nm) light once every minute for 1 hour, (2) 131 W/m² of green (λ_max ≈ 527 nm) light, continuously on for 1 hour, and (3) 2-second flashes of the same green light once every minute for 1 hour. Inferential statistics showed that the blue flash light-stimulus condition significantly delayed circadian phase and significantly suppressed nocturnal melatonin. The results of this study further our basic understanding of circadian phototransduction and broaden the technical foundations for delivering light through closed eyelids during sleep for treating circadian sleep disorders.

Keywords:

• melatonin
• dim light melatonin onset
• eyelids
• flashing blue light
• circadian rhythms
• sleep

Acknowledgments

This study was funded by Philips Respironics. The authors would like to thank Michael Colbaugh, Nathan Zimmerman, and Doug Mechlenburg from Philips Respironics for their support. The authors would also like to acknowledge Barbara Plitnick, Brittany Wood, Anna Lok, Robert Hamner, Sharon Lesage, Kenneth Appleman, Rebekah Mullaney, Ines Martinovic, and Dennis Guyon from the Lighting Research Center for their technical and editorial support.

Disclosure

The authors have jointly filed patent applications related to this work with Philips Respironics. The authors report no other conflicts of interest in this work.