The Circadian Response of Intrinsically Photosensitive Retinal Ganglion Cells

• Published in: PloS one Vol. 6; no. 3; p. e17860
• Main Authors: Zele, Andrew J., Feigl, Beatrix, Smith, Simon S., Markwell, Emma L.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 14.03.2011; Public Library of Science (PLoS)
• Subjects: Adolescent; Adult; Age; Ambient temperature; Biology; Caffeine; Cataracts; Circadian rhythm; Circadian Rhythm - radiation effects; Circadian rhythms; CLOCK protein; Cones; Cues; Entrainment; Eye diseases; Female; Ganglion cysts; Human subjects; Humans; Illumination; Light; Light effects; Male; Melanopsin; Melatonin; Melatonin - metabolism; Optometry; Photoreceptors; Photosensitivity; Posture; Pupil - radiation effects; Reflex - radiation effects; Reflexes; Retina; Retinal Cone Photoreceptor Cells - physiology; Retinal Cone Photoreceptor Cells - radiation effects; Retinal ganglion cells; Retinal Ganglion Cells - physiology; Retinal Ganglion Cells - radiation effects; Saliva - metabolism; Sleep; Sleep disorders; Temperature effects; Time Factors; Variation; Young Adult; Australia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0017860

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.