Effect of Single and Combined Monochromatic Light on the Human Pupillary Light Response.

The pupillary light reflex (PLR) is a neurological reflex driven by rods, cones, and melanopsin-containing retinal ganglion cells. Our aim was to achieve a more precise picture of the effects of 5-min duration monochromatic light stimuli, alone or in combination, on the human PLR, to determine its spectral sensitivity and to assess the importance of photon flux. Using pupillometry, the PLR was assessed in 13 participants (6 women) aged 27.2 ± 5.41 years (mean ± SD) during 5-min light stimuli of purple (437 nm), blue (479 nm), red (627 nm), and combinations of red+purple or red+blue light. In addition, nine 5-min, photon-matched light stimuli, ranging in 10 nm increments peaking between 420 and 500 nm were tested in 15 participants (8 women) aged 25.7 ± 8.90 years. Maximum pupil constriction, time to achieve this, constriction velocity, area under the curve (AUC) at short (0-60 s), and longer duration (240-300 s) light exposures, and 6-s post-illumination pupillary response (6-s PIPR) were assessed. Photoreceptor activation was estimated by mathematical modeling. The velocity of constriction was significantly faster with blue monochromatic light than with red or purple light. Within the blue light spectrum (between 420 and 500 nm), the velocity of constriction was significantly faster with the 480 nm light stimulus, while the slowest pupil constriction was observed with 430 nm light. Maximum pupil constriction was achieved with 470 nm light, and the greatest AUC0-60 and AUC240-300 was observed with 490 and 460 nm light, respectively. The 6-s PIPR was maximum after 490 nm light stimulus. Both the transient (AUC0-60) and sustained (AUC240-300) response was significantly correlated with melanopic activation. Higher photon fluxes for both purple and blue light produced greater amplitude sustained pupillary constriction. The findings confirm human PLR dependence on wavelength, monochromatic or bichromatic light and photon flux under 5-min duration light stimuli. Since the most rapid and high amplitude PLR occurred within the 460-490 nm light range (alone or combined), our results suggest that color discrimination should be studied under total or partial substitution of this blue light range (460-490 nm) by shorter wavelengths (~440 nm). Thus for nocturnal lighting, replacement of blue light with purple light might be a plausible solution to preserve color discrimination while minimizing melanopic activation.

Disruption of Circadian Rhythms and Delirium, Sleep Impairment and Sepsis in Critically ill Patients. Potential Therapeutic Implications for Increased Light-Dark Contrast and Melatonin Therapy in an ICU Environment.

The confinement of critically ill patients in intensive care units (ICU) imposes environmental constancy throughout both day and night (continuous light, noise, caring activities medications, etc.), which has a negative impact on human health by inducing a new syndrome known as circadian misalignment, circadian disruption or chronodisruption (CD). This syndrome contributes to poor sleep quality and delirium, and may impair septic states frequently observed in critically ill patients. However, and although the bidirectional crosstalk between CD with sleep impairment, delirium and inflammation in animal models has been known for years and has been suspected in ICU patients, few changes have been introduced in the environment and management of ICU patients to improve their circadian rhythmicity. Delirium, the most serious condition because it has a severe effect on prognosis and increases mortality, as well as sleep impairment and sepsis, all three of them linked to disorganization of the circadian system in critically ill patients, will be revised considering the functional organization of the circadian system, the main input and output signals that synchronize the clock, including a brief description of the molecular circadian clock machinery, the non-visual effects of light, and the ICU light environment. Finally, the potential usefulness of increased light/dark contrast and melatonin treatment in this context will be analyzed, including some practical countermeasures to minimize circadian disruption and improve circadian system chronoenhancement, helping to make these units optimal healing environments for patients.

Period gene expression in the brain of a dual-phasing rodent, the Octodon degus.

Clock gene expression is not only confined to the master circadian clock in the suprachiasmatic nucleus (SCN) but is also found in many other brain regions. The phase relationship between SCN and extra-SCN oscillators may contribute to known differences in chronotypes. The Octodon degus is a diurnal rodent that can shift its activity-phase preference from diurnal to nocturnal when running wheels become available. To understand better the relationship between brain clock gene activity and chronotype, we studied the day-night expression of the Period genes, Per1 and Per2, in the SCN and extra-SCN brain areas in diurnal and nocturnal degus. Since negative masking to light and entrainment to the dark phase are involved in the nocturnalism of this species, we also compare, for the first time, Per expression between entrained (EN) and masked nocturnal (MN) degus. The brains of diurnal, MN, and EN degus housed with wheels were collected during the light (ZT4) and dark (ZT16) phases. Per1 and Per2 mRNA levels were analyzed by in situ hybridization. Within the SCN, signals for Per1 and Per2 were higher at ZT4 irrespective of chronotype. However, outside of the SCN, Per1 expression in the hippocampus of EN degus was out of phase (higher values at ZT16) with SCN values. Although a similar trend was seen in MN animals, this day-night difference in Per1 expression was not significant. Interestingly, daily differences in Per1 expression were not seen in the hippocampus of diurnal degus. For other putative brain areas analyzed (cortices, striatum, arcuate, ventromedial hypothalamus), no differences in Per1 levels were found between chronotypes. Both in diurnal and nocturnal degus, Per2 levels in the hippocampus and in the cingulate and piriform cortices were in phase with their activity rhythms. Thus, diurnal degus showed higher Per2 levels at ZT4, whereas in both types of nocturnal degus, Per2 expression was reversed, peaking at ZT16. Together, the present study supports the hypothesis that the mechanisms underlying activity-phase preference in diurnal and nocturnal mammals reside downstream from the SCN, but our data also indicate that there are fundamental differences between nocturnal masked and entrained degus.