Relationship between Human Pupillary Light Reflex and Circadian System Status

PLoS One. 2016 Sep 16;11(9):e0162476. doi: 10.1371/journal.pone.0162476. eCollection 2016.

Abstract

Intrinsically photosensitive retinal ganglion cells (ipRGCs), whose photopigment melanopsin has a peak of sensitivity in the short wavelength range of the spectrum, constitute a common light input pathway to the olivary pretectal nucleus (OPN), the pupillary light reflex (PLR) regulatory centre, and to the suprachiasmatic nuclei (SCN), the major pacemaker of the circadian system. Thus, evaluating PLR under short wavelength light (λmax ≤ 500 nm) and creating an integrated PLR parameter, as a possible tool to indirectly assess the status of the circadian system, becomes of interest. Nine monochromatic, photon-matched light stimuli (300 s), in 10 nm increments from λmax 420 to 500 nm were administered to 15 healthy young participants (8 females), analyzing: i) the PLR; ii) wrist temperature (WT) and motor activity rhythms (WA), iii) light exposure (L) pattern and iv) diurnal preference (Horne-Östberg), sleep quality (Pittsburgh) and daytime sleepiness (Epworth). Linear correlations between the different PLR parameters and circadian status index obtained from WT, WA and L recordings and scores from questionnaires were calculated. In summary, we found markers of robust circadian rhythms, namely high stability, reduced fragmentation, high amplitude, phase advance and low internal desynchronization, were correlated with a reduced PLR to 460-490 nm wavelengths. Integrated circadian (CSI) and PLR (cp-PLR) parameters are proposed, that also showed an inverse correlation. These results demonstrate, for the first time, the existence of a close relationship between the circadian system robustness and the pupillary reflex response, two non-visual functions primarily under melanopsin-ipRGC input.

MeSH terms

  • Circadian Rhythm*
  • Humans
  • Light Signal Transduction
  • Light*
  • Motor Activity
  • Pupil / physiology*
  • Reflex, Pupillary
  • Suprachiasmatic Nucleus / physiology

Grants and funding

The authors wish to thank the Instituto de Salud Carlos III, the Spanish Ministry of Science and Innovation and the Ministry of Economy and Competitiveness for their financial support through the Spanish Network for Light Pollution Studies (AYA2015-71542-REDT), the Ageing and Frailty Cooperative Research Network, RD12/0043/0011, SAF2013-49132-C2-1-R, the latter including FEDER cofunding granted to Juan Antonio Madrid, and Seneca Foundation 19410/PI/14 to Maria Angeles Rol. Research fellowship granted to MA Bonmatí (AP2009-1051). The work was parted funded by an EPSRC MILES grant [EP/1000992/1]. S. J. Sweeney gratefully acknowledges EPSRC Leadership Fellowship funding under project EP/H005587/1. D. J. Skene is a Royal Society Wolfson Research Merit Award holder.