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The Effects of Short-Term Light Adaptation on the Human Post-Illumination Pupil Response

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The Effects of Short-Term Light Adaptation on the Human Post-Illumination Pupil Response Visual Neuroscience The Effects of Short-Term Light Adaptation on the Human Post-Illumination Pupil Response Daniel S. Joyce,1,2 Beatrix Feigl,1,3,4 and Andrew J. Zele1,2 1Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, Australia 2Visual Science Laboratory, School of Optometry and Vision Science, Queensland University of Technology (QUT), Brisbane, Australia 3Medical Retina Laboratory, School of Biomedical Sciences, Queensland University of Technology (QUT), Brisbane, Australia 4Queensland Eye Institute, Brisbane, Australia Correspondence: Andrew J. Zele, PURPOSE. We determine the effect of short-term light adaptation on the pupil light reflex and Visual Science Laboratory, Institute the melanopsin mediated post-illumination pupil response (PIPR). Inner and outer retinal of Health and Biomedical photoreceptor contributions to the dark-adapted pupil response were estimated. Innovation, 60 Musk Avenue, Kelvin Grove, Queensland 4059, Australia; METHODS. In Experiment A, light adaptation was studied using short wavelength lights ranging [email protected]. from subthreshold to suprathreshold irradiances for melanopsin signaling that were Submitted: May 15, 2016 presented before (5–60 seconds) and after (30 seconds) a melanopsin-exciting stimulus Accepted: September 2, 2016 pulse. We quantified the pupil constriction and the poststimulus response amplitudes during dark (PIPR) and light (poststimulus pupil response, PSPR) adaptation. In Experiment B, Citation: Joyce DS, Feigl B, Zele AJ. colored prestimulus adapting lights were univariant for melanopsin or rod excitation. The effects of short-term light adaptation on the human post- RESULTS. Increasing the prestimulus duration and irradiance of adapting lights increased the illumination pupil response. Invest pupil constriction amplitude when normalized to the dark-adapted baseline but reduced its Ophthalmol Vis Sci. 2016;57:5672– amplitude when normalized to the light-adapted baseline. Light adaptation at irradiances 5680. DOI:10.1167/iovs.16-19934 suprathreshold for melanopsin activation increased the PIPR amplitude, with larger changes at longer adaptation durations, whereas the PSPR amplitude became more attenuated with increasing irradiances, independent of duration. Rod versus melanospin univariant adaptation did not alter the constriction amplitude but increased the PIPR amplitude in the rod condition. Correlations between millimeter pupil constriction and PIPR amplitudes were eliminated when normalized to the baseline diameter. CONCLUSIONS. The findings have implications for standardizing light adaptation paradigms and the choice of pupil metrics in both laboratory and clinical settings. Light and dark adaptation have opposite effects on the pupil metrics, which should be normalized to baseline to minimize significant correlations between constriction and PIPR amplitudes. Keywords: pupil, melanopsin, adaptation ntrinsically photosensitive retinal ganglion cells (ipRGC) stimulus light with high-melanopsin excitation.17 Preadaptation I project to over a dozen brain regions1–8 including the olivary for 10 minutes to photopic broadband light (30 cd.mÀ2) pretectal nucleus (OPN), which controls the pupil response.9 attenuates the PIPR amplitude measured in the dark in Intrinsically photosensitive RGCs receive extrinsic synaptic response to a melanopsin-exciting stimulus pulse, with the inputs from outer retinal rod and cone photoreceptors, as well PIPR gradually recovering and plateauing 20-minutes postadap- as signal intrinsically via the photopigment melanopsin.3,10,11 tation.18 Studies have demonstrated complete attenuation of The pupil light reflex (PLR) therefore provides an objective and the PIPR amplitude during continuous adaptation to blue light noninvasive measure of the functional correlates of both designed to desensitize rods,19,20 but the causal mechanism for extrinsic and intrinsic ipRGC signaling in humans. Under this attenuation is unknown and may be due to incomplete dark-adapted conditions it is known that ipRGCs primarily melanopsin adaptation given that the PIPR mainly reflects control the post-illumination pupil response (PIPR) in hu- melanopsin signaling,12–15 at least under dark-adapted condi- mans12–14 and nonhuman primates14 from at least 1.7 seconds tions. post-illumination,15 because the PIPR spectral sensitivity We propose that light adaptation may affect the PIPR matches that of the melanopsin nomogram.3,15 It is largely amplitude due to the different temporal dynamics and light unknown how light adaptation affects the PIPR amplitude. adaptation characteristics of the extrinsic and intrinsic ipRGC Light adaptation alters the steady-state pupil constriction: pathways as observed in electrophysiological recordings.3,21–23 The constriction amplitude increases when assessed 40 We systematically examine how light adaptation affects the minutes after a 5 minute pre-exposure to long wavelength pupil constriction amplitude (reflecting both extrinsic þ light with low-melanopsin excitation.16 Preadaptation to 30 intrinsic ipRGC contributions) and the PIPR amplitude seconds of short- or long-wavelength light also increases the (reflecting intrinsic ipRGC contributions) by altering the subsequent steady-state pupil constriction amplitude to a blue- duration and irradiance of a short-wavelength adapting field iovs.arvojournals.org j ISSN: 1552-5783 5672 This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. Downloaded from iovs.arvojournals.org on 10/02/2021 Adaptation and the Post-Illumination Pupil Response IOVS j October 2016 j Vol. 57 j No. 13 j 5673 presented pre- and poststimulus to a pulse with high- normalizing the data to the baseline (light adapted) pupil melanopsin excitation (Experiment A). Because steady-state diameter, rather than to its dark-adapted baseline, we analyze pupil control is dominated by the activity of extrinsic rod and the pupil metrics normalized to both the dark and light intrinsic melanopsin contributions,24 we determined how the adapted baseline diameters (see the Analyses section). The constriction and PIPR amplitudes are altered by fixing the paradigm for Experiment A consisted of a 10-second dark- excitations of these photoreceptor classes (Experiment B). adapted baseline, 5 to 60 seconds prestimulus light adaptation, the 1-second stimulus pulse, 30 seconds of continued light adaptation, and a 40 second PIPR measured after offset of the METHODS adapting field (see schematic in Fig. 1A). Three repeats of each condition were obtained for two observers. Participants To examine interactions between extrinsic and intrinsic Experiment A included two participants (1 male age 33 and 1 signal contributions to the pupil light reflex, Experiment B female age 40) and Experiment B included four males (mean investigated the dark adapted pupil constriction and PIPR age 31.8, SD 0.5). Ophthalmologic examination (slit-lamp amplitudes after exposure to prestimulus adapting fields that examination, IOP with tonometry [Icare, Vantaa, Finland], altered the (1) color (blue, cyan, green), (2) duration (1, 3, 5 ophthalmoscopy, color vision [desaturated Lanthony D15] and seconds), (3) irradiance (10.5, 11.5, 12.5, 13.5 log photo- À2 À1 optical coherence tomography [OCT; Cirrus HD-OCT; Carl ns.cm .s , but see next paragraph), and (4) photoreceptor Zeiss Meditec, Dublin, CA, USA]) confirmed all participants univariance (melanopsin, rods) of the adapting fields. had normal eye health. Participants had a best-corrected visual Adapting field durations and irradiances were selected acuity of 6/6 or greater (Bailey Lovie chart). The University’s based upon the physiological temporal signaling characteristics Human Research Ethics Committee (ethics number (latency and time to peak) of the extrinsic and intrinsic ipRGC 3,4,21–23 1400000842) approved the experiment, which was conducted pathways, spanning the mesopic to photopic light 3,21 in accordance with the Code of Ethics of the World Medical levels of their signaling range. For each colored field, the Association (Declaration of Helsinki). Informed consent was light levels were specified relative to the peak spectral obtained from participants before the experiment began. sensitivity of melanopsin or rods for the four irradiances; therefore, these irradiances as expressed are indicative only and will underestimate the true irradiance of each field as none Apparatus of the primaries had a kmax of 482 or 507 nm. The green 13.5 Pupillometry stimuli were generated using a custom-built log photons.cmÀ2.sÀ1 condition was not generated because of Maxwellian-view optical system with three light-emitting diode the low peak irradiance output of the green primary. primary lights (5 mm; ‘blue’ kmax 464 nm, full width at half Melanopsin or rod univariance was maintained across the maximum (FWHM); 26 nm, ‘cyan’ kmax 512 nm, FWHM 32 nm; three adapting field wavelengths by adjusting the irradiance of and ‘green’ kmax 560 nm, FWHM 12 nm; measured with a each blue, cyan, and green primary light based upon the StellarNet EPC200C spectroradiometer, Tampa, FL, USA). The spectral profile of each primary in conjunction with the known light from the primaries was spatially homogenized with 58 spectral sensitivities of melanopsin inputs to the PIPR (kmax 12–14,25 light shaping diffusers (Physical Optics Corp., Torrance, CA, 482 nm and rod inputs to image forming vision (kmax USA) then focused through achromat doublet lenses (Edmund
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