Circadian and wake-dependent effects on the pupil light reflex in response to narrow-bandwidth light pulses.
OBJECTIVE
Nonvisual light-dependent functions in humans are conveyed mainly by intrinsically photosensitive retinal ganglion cells, which express melanopsin as photopigment. We aimed to identify the effects of circadian phase and sleepiness across 24 hours on various aspects of the pupil response to light stimulation.


METHODS
We tested 10 healthy adults hourly in two 12-hour sessions covering a 24-hour period. Pupil responses to narrow bandwidth red (635 ± 18 nm) and blue (463 ± 24 nm) light (duration of 1 and 30 seconds) at equal photon fluxes were recorded, and correlated with salivary melatonin concentrations at the same circadian phases and to subjective sleepiness ratings. The magnitude of pupil constriction was determined from minimal pupil size. The post-stimulus pupil response was assessed from the pupil size at 6 seconds following light offset, the area within the redilation curve, and the exponential rate of redilation.


RESULTS
Among the measured parameters, the pupil size 6 seconds after light offset correlated with melatonin concentrations (P < 0.05) and showed a significant modulation over 24 hours with maximal values after the nocturnal peak of melatonin secretion. In contrast, the post-stimulus pupil response following red light stimulation correlated with subjective sleepiness (P < 0.05) without significant changes over 24 hours.


CONCLUSIONS
The post-stimulus pupil response to blue light as a marker of intrinsic melanopsin activity demonstrated a circadian modulation. In contrast, the effect of sleepiness was more apparent in the cone contribution to the pupil response. Thus, pupillary responsiveness to light is under influence of the endogenous circadian clock and subjective sleepiness.
Solar Energy and Building Physics Laboratory, ENAC, Swiss Federal Institute of Technology, Lausanne, Switzerland.
Mirjam
M
Münch
Lorette
L
Léon
Sylvain V
SV
Crippa
Aki
A
Kawasaki
D002940:Circadian Rhythm / Q000502:physiology*; D005260:Female; D006801:Humans; D008027:Light; D008297:Male; D008550:Melatonin / Q000378:metabolism; D011680:Pupil / Q000528:radiation effects*; D011863:Radioimmunoassay; D012025:Reflex, Pupillary / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000502:physiology / Q000528:radiation effects; D017299:Rod Opsins / Q000378:metabolism; D012463:Saliva / Q000378:metabolism; D012890:Sleep / Q000502:physiology; D055815:Young Adult; D000099210:Melanopsin
D008550:Melatonin; D017299:Rod Opsins; D000099210:Melanopsin