ABSTRACT
Intrinsically photosensitive retinal ganglion cells (ipRGC) signal environmental
light level to the central circadian clock and contribute to the pupil light
reflex. It is unknown if ipRGC activity is subject to extrinsic (central) or
intrinsic (retinal) network-mediated circadian modulation during light
entrainment and phase shifting. Eleven younger persons (18–30 years) with
no ophthalmological, medical or sleep disorders participated. The activity of
the inner (ipRGC) and outer retina (cone photoreceptors) was assessed hourly
using the pupil light reflex during a 24 h period of constant environmental
illumination (10 lux). Exogenous circadian cues of activity, sleep, posture,
caffeine, ambient temperature, caloric intake and ambient illumination were
controlled. Dim-light melatonin onset (DLMO) was determined from salivary
melatonin assay at hourly intervals, and participant melatonin onset values were
set to 14 h to adjust clock time to circadian time. Here we demonstrate in
humans that the ipRGC controlled post-illumination pupil response has a
circadian rhythm independent of external light cues. This circadian variation
precedes melatonin onset and the minimum ipRGC driven pupil response occurs post
melatonin onset. Outer retinal photoreceptor contributions to the inner retinal
ipRGC driven post-illumination pupil response also show circadian variation
whereas direct outer retinal cone inputs to the pupil light reflex do not,
indicating that intrinsically photosensitive (melanopsin) retinal ganglion cells
mediate this circadian variation.
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Publisher: Public Library of Science
Date Published: 14-March-2011
Author(s): Zele A., Feigl B., Smith S., Markwell E.
Link: https://doi.org/10.1371/journal.pone.0017860