title: Post-illumination pupil response after blue light: Reliability of optimized melanopsin-based phototransduction assessment.
abstract: Melanopsin-containing retinal ganglion cells have recently been shown highly relevant to the non-image forming effects of light, through their direct projections on brain circuits that regulate alertness, mood and circadian rhythms. A quantitative assessment of functionality of the melanopsin-signaling pathway could be highly relevant in order to mechanistically understand individual differences in the effects of light on these regulatory systems. We here propose and validate a reliable quantification of the melanopsin-dependent Post-Illumination Pupil Response (PIPR) after blue light, and evaluated its sensitivity to dark adaptation, time of day, body posture, and light exposure history. Pupil diameter of the left eye was continuously measured during a series of light exposures to the right eye, of which the pupil was dilated using tropicamide 0.5%. The light exposure paradigm consisted of the following five consecutive blocks of five minutes: baseline dark; monochromatic red light (peak wavelength: 630 nm, luminance: 375 cd/m(2)) to maximize the effect of subsequent blue light; dark; monochromatic blue light (peak wavelength: 470 nm, luminance: 375 cd/m(2)); and post-blue dark. PIPR was quantified as the difference between baseline dark pupil diameter and post-blue dark pupil diameter (PIPR-mm). In addition, a relative PIPR was calculated by dividing PIPR by baseline pupil diameter (PIPR-%). In total 54 PIPR assessments were obtained in 25 healthy young adults (10 males, mean age ± SD: 26.9 ± 4.0 yr). From repeated measurements on two consecutive days in 15 of the 25 participants (6 males, mean age ± SD: 27.8 ± 4.3 yrs) test-retest reliability of both PIPR outcome parameters was calculated. In the presence of considerable between-subject differences, both outcome parameters had very high test-retest reliability: Cronbach's α > 0.90 and Intraclass Correlation Coefficient > 0.85. In 12 of the 25 participants (6 males, mean age ± SD: 26.5 ± 3.6 yr) we examined the potential confounding effects of dark adaptation, time of the day (morning vs. afternoon), body posture (upright vs. supine position), and 24-h environmental light history on the PIPR assessment. Mixed effect regression models were used to analyze these possible confounders. A supine position caused larger PIPR-mm (β = 0.29 mm, SE = 0.10, p = 0.01) and PIPR-% (β = 4.34%, SE = 1.69, p = 0.02), which was due to an increase in baseline dark pupil diameter; this finding is of relevance for studies requiring a supine posture, as in functional Magnetic Resonance Imaging, constant routine protocols, and bed-ridden patients. There were no effects of dark adaptation, time of day, and light history. In conclusion, the presented method provides a reliable and robust assessment of the PIPR to allow for studies on individual differences in melanopsin-based phototransduction and effects of interventions.
authors.affiliation: Netherlands Institute for Neuroscience, Dept. Sleep and Cognition, Amsterdam, The Netherlands. Electronic address: w.van.der.meijden@nin.knaw.nl.
authors.forename: Wisse P
authors.initials: WP
authors.lastname: van der Meijden
authors.affiliation: Netherlands Institute for Neuroscience, Dept. Sleep and Cognition, Amsterdam, The Netherlands.
authors.forename: Bart H W
authors.initials: BH
authors.lastname: te Lindert
authors.affiliation: PsyQ Psycho-Medical Programs, Program Adult ADHD, The Hague, The Netherlands.
authors.forename: Denise
authors.initials: D
authors.lastname: Bijlenga
authors.affiliation: Netherlands Institute for Neuroscience, Dept. Sleep and Cognition, Amsterdam, The Netherlands.
authors.forename: Joris E
authors.initials: JE
authors.lastname: Coppens
authors.affiliation: Netherlands Institute for Neuroscience, Dept. Sleep and Cognition, Amsterdam, The Netherlands.
authors.forename: Germán
authors.initials: G
authors.lastname: Gómez-Herrero
authors.affiliation: Netherlands Institute for Neuroscience, Dept. Sleep and Cognition, Amsterdam, The Netherlands.
authors.forename: Jessica
authors.initials: J
authors.lastname: Bruijel
authors.affiliation: PsyQ Psycho-Medical Programs, Program Adult ADHD, The Hague, The Netherlands.
authors.forename: J J Sandra
authors.initials: JJ
authors.lastname: Kooij
authors.affiliation: Center for Chronobiology, Psychiatric Hospital of the University of Basel, Basel, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Cajochen
authors.affiliation: Sleep Disorders Center, CHU and FMTS, CNRS-UPR 3212, Institute of Cellular and Integrative Neurosciences, University of Strasbourg, Strasbourg, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Bourgin
authors.affiliation: Netherlands Institute for Neuroscience, Dept. Sleep and Cognition, Amsterdam, The Netherlands; Depts. of Integrative Neurophysiology and Medical Psychology, Center for Neurogenomics and Cognitive Research (CNCR), Neuroscience Campus Amsterdam, VU University and Medical Center, Amsterdam, The Netherlands.
authors.forename: Eus J W
authors.initials: EJ
authors.lastname: Van Someren
mesh_terms: D000328:Adult; D002940:Circadian Rhythm; D003623:Dark Adaptation; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008027:Light; D055537:Light Signal Transduction / Q000502:physiology* / Q000528:radiation effects; D008297:Male; D010775:Photic Stimulation; D012025:Reflex, Pupillary / Q000502:physiology*; D015203:Reproducibility of Results; D012165:Retinal Ganglion Cells / Q000378:metabolism*; D017299:Rod Opsins; D000099210:Melanopsin
chemical_list: D017299:Rod Opsins; D000099210:Melanopsin
keywords: Intrinsically photosensitive retinal ganglion cells; Light; Melanopsin; Pupil; Test-retest reliability