Relationship between Human Pupillary Light Reflex and Circadian System Status (original) (raw)
Related papers
Human Retinal Light Sensitivity and Melatonin Rhythms Following Four Days in Near Darkness
Chronobiology International, 2009
The rods in the retina are responsible for night vision, whereas the cone system enables day vision. We studied whether rod function in humans exhibits an endogenous circadian rhythm and if changes occur in conditions of prolonged darkness. Seven healthy subjects (mean age + SD: 25.6 + 12.3 yr) completed a 4.5-day protocol during which they were kept in complete darkness (days 1 and 4) and near darkness (,0.1 lux red light, days 2 and 3). Electroretinography (ERG) and saliva collections were done at intervals of at least 3 h for 27 h on days 1 and 4. Full-field ERGs were recorded over 10 low-intensity green light flashes known to test predominantly rod function. As a circadian marker, salivary melatonin concentration was measured by radioimmunoassay. The ERG data showed that rod responsiveness to light progressively diminished in darkness (significantly lower a-and b-wave amplitudes, longer b-wave implicit time). The decrease in amplitude (b-wave) from day 1 to day 4 averaged 22 + 14%. After correction for the darkness-related linear trend, the circadian variations in ERG indices were weak and usually non-significant, with slightly higher responsiveness to light during the day than night. Rod sensitivity (by K index) tended to decrease. Strikingly, the overall amount of melatonin secretion (area under 24 h curve) also decreased from day 1 to day 4 by 33.1 + 18.9% ( p ¼ .017). The drift of the melatonin rhythm phase was within the normal range, less than 56 min over three days. There was no significant correlation between the changes in ERG responses and melatonin. In conclusion, scotopic retinal response to (low-intensity) light and the amount of melatonin secreted
Human Cone Light Sensitivity and Melatonin Rhythms Following 24-hour Continuous Illumination
Chronobiology International, 2011
This study investigates the possibility of an endogenous circadian rhythm in retinal cone function in humans. A full-field cone electroretinogram (ERG) was performed every 2 h for 24 h under continuous rod-saturating ambient white light (53 ± 30 lux; pupils dilated) in nine healthy subjects. Distinct circadian variations were superimposed upon a gradual decrease in cone responsiveness to light, demonstrated most reliably in the implicit times of b-wave and oscillatory potentials, and to a lesser extent in amplitude and a-wave implicit times. After mathematical correction of the linear trend, the cone response was found to be greatest around 20:00 h and least around 06:00 h. The phase of the ERG circadian rhythm was not synchronized with the phase of the salivary melatonin rhythm measured the previous evening. Melatonin levels measured under constant light on the day of ERG assessments were suppressed by 53% on average compared to melatonin profiles obtained previously under near-total darkness in seven participants. The progressive decline in cone responsiveness to light over the 24 h may reflect an adaptation of the cone-driven retinal system to constant light, although the mechanism is unclear. The endogenous rhythm of cone responsiveness to light may be used as an additional index of central or retinal circadian clock time. (Author correspondence: kvdani@mail.ru)
Journal of Biological Rhythms, 2019
Nighttime melatonin suppression is the most commonly used method to indirectly quantify acute nonvisual light effects. Since light is the principal zeitgeber in humans, there is a need to assess its strength during daytime as well. This is especially important since humans evolved under natural daylight but now often spend their time indoors under artificial light, resulting in a different quality and quantity of light. We tested whether the pupillary light response (PLR) could be used as a marker for nonvisual light effects during daytime. We also recorded the wake electroencephalogram to objectively determine changes in daytime sleepiness between different illuminance levels and/or spectral compositions of light. In total, 72 participants visited the laboratory 4 times for 3-h light exposures. All participants underwent a dim-light condition and either 3 metameric daytime light exposures with different spectral compositions of polychromatic white light (100 photopic lux, peak wavelengths at 435 nm or 480 nm, enriched with longer wavelengths of light) or 3 different illuminances (200, 600, and 1200 photopic lux) with 1 metameric lighting condition (peak wavelength at 435 nm or 480 nm; 24 participants each). The results show that the PLR was sensitive to both spectral differences between metameric lighting conditions and different illuminances in a dose-responsive manner, depending on melanopic irradiance. Objective sleepiness was significantly reduced, depending on melanopic irradiance, at low illuminance (100 lux) and showed fewer differences at higher illuminance. Since many people are exposed to such low illuminance for most of their day-living in biological darkness-our results imply that optimizing the light spectrum could be important to improve daytime alertness. Our results 2 JOURNAL OF BIOLOGICAL RHYTHMS / Month 201X suggest the PLR as a noninvasive physiological marker for ambient light exposure effects during daytime. These findings may be applied to assess lightdependent zeitgeber strength and evaluate lighting improvements at workplaces, schools, hospitals, and homes.
Preliminary evidence for a change in spectral sensitivity of the circadian system at night
Journal of Circadian Rhythms, 2005
Background It is well established that the absolute sensitivity of the suprachiasmatic nucleus to photic stimulation received through the retino-hypothalamic tract changes throughout the 24-hour day. It is also believed that a combination of classical photoreceptors (rods and cones) and melanopsin-containing retinal ganglion cells participate in circadian phototransduction, with a spectral sensitivity peaking between 440 and 500 nm. It is still unknown, however, whether the spectral sensitivity of the circadian system also changes throughout the solar day. Reported here is a new study that was designed to determine whether the spectral sensitivity of the circadian retinal phototransduction mechanism, measured through melatonin suppression and iris constriction, varies at night. Methods Human adult males were exposed to a high-pressure mercury lamp [450 lux (170 μW/cm2) at the cornea] and an array of blue light emitting diodes [18 lux (29 μW/cm2) at the cornea] during two nighttime experimental sessions. Both melatonin suppression and iris constriction were measured during and after a one-hour light exposure just after midnight and just before dawn. Results An increase in the percentage of melatonin suppression and an increase in pupil constriction for the mercury source relative to the blue light source at night were found, suggesting a temporal change in the contribution of photoreceptor mechanisms leading to melatonin suppression and, possibly, iris constriction by light in humans. Conclusion The preliminary data presented here suggest a change in the spectral sensitivity of circadian phototransduction mechanisms at two different times of the night. These findings are hypothesized to be the result of a change in the sensitivity of the melanopsin-expressing retinal ganglion cells to light during the night.
Journal of Biological Rhythms, 2005
The mammalian retina contains both visual and circadian photoreceptors. In humans nocturnal stimulation of the latter receptors leads to melatonin suppression, which might cause reduced nighttime sleepiness. Melatonin suppression is maximal when the nasal part of the retina is illuminated. Whether circadian phase shifting in humans is due to the same photoreceptors is not known. We here explore whether phase shifts and melatonin suppression depend on the same retinal area. Twelve healthy subjects participated in a within-subjects design and received all of three light conditions -(1) 10 lux of dim light on the whole retina, (2) 100 lux of ocular light on the nasal part of the retina, and (3) 100 lux of ocular light on the temporal part of the retina-on separate nights in random order. In all three conditions pupils were dilated before and during light exposure. The protocol consisted of an adaptation night followed by a 23-h period of sustained wakefulness, during which a 4-h light pulse was presented at a time when maximal phase delays were expected. Nasal illumination resulted in an immediate suppression of melatonin, but had no effect on subjective sleepiness or core body temperature (CBT). Nasal illumination delayed the subsequent melatonin rhythm by 78 min, which is significantly (p = 0.016) more than the delay drift in the dim light condition (38 min), but had no detectable phase shifting effect on the CBT rhythm. Temporal illumination suppressed melatonin less than the nasal illumination and had no effect on subjective sleepiness and CBT. Temporal illumination delayed neither the melatonin rhythm nor the CBT rhythm. The data show that the suppression of melatonin does not necessarily result in a reduction of subjective sleepiness and an elevation of CBT. 100 lux of bright white light is strong enough to affect the photoreceptors responsible for the suppression of melatonin, but not strong enough to have a significant effect on sleepiness and CBT. This may be due to the larger variability of the latter variables.
Melatonin Suppression by Light in Humans Is Maximal When the Nasal Part of the Retina Is Illuminated
Journal of Biological Rhythms, 1999
This study investigated whether sensitivity of the nocturnal melatonin suppression response to light depends on the area of the retina exposed. The reason to suspect uneven spatial sensitivity distribution stems from animal work that revealed that retinal ganglion cells projecting to the suprachiasmatic nuclei (SCN) are unequally distributed in several species of mammals. Four distinct areas of the retinas of 8 volunteers were selectively exposed to 500 lux between 1:30 a.m. and 3:30 a.m. Saliva samples were taken before, during, and after light exposure in 1-h intervals. A significant difference in sensitivity was found between exposure of the lateral and nasal parts of the retinas, showing that melatonin suppression is maximal on exposure of the nasal part of the retina. The results imply that artificial manipulation of the circadian pacemaker to alleviate jet lag, to improve alertness in shift workers, and possibly to treat patients suffering from seasonal affective disorder shou...
Chronobiology International, 2014
Light is an important environmental stimulus for the entrainment of the circadian clock and for increasing alertness. The intrinsically photosensitive ganglion cells in the retina play an important role in transferring this light information to the circadian system and they are elicited in particular by short-wavelength light. Exposure to short wavelengths is reduced, for instance, in elderly people due to yellowing of the ocular lenses. This reduction may be involved in the disrupted circadian rhythms observed in aged subjects. Here, we tested the effects of reduced blue light exposure in young healthy subjects (n ¼ 15) by using soft orange contact lenses (SOCL). We showed (as expected) that a reduction in the melatonin suppressing effect of light is observed when subjects wear the SOCL. However, after chronic exposure to reduced (short wavelength) light for two consecutive weeks we observed an increase in sensitivity of the melatonin suppression response. The response normalized as if it took place under a polychromatic light pulse. No differences were found in the dim light melatonin onset or in the amplitude of the melatonin rhythms after chronic reduced blue light exposure. The effects on sleep parameters were limited. Our results demonstrate that the non-visual light system of healthy young subjects is capable of adapting to changes in the spectral composition of environmental light exposure. The present results emphasize the importance of considering not only the short-term effects of changes in environmental light characteristics.
Circadian Photoentrainment in Mice and Humans
Biology, 2020
Light around twilight provides the primary entrainment signal for circadian rhythms. Here we review the mechanisms and responses of the mouse and human circadian systems to light. Both utilize a network of photosensitive retinal ganglion cells (pRGCs) expressing the photopigment melanopsin (OPN4). In both species action spectra and functional expression of OPN4 in vitro show that melanopsin has a λmax close to 480 nm. Anatomical findings demonstrate that there are multiple pRGC sub-types, with some evidence in mice, but little in humans, regarding their roles in regulating physiology and behavior. Studies in mice, non-human primates and humans, show that rods and cones project to and can modulate the light responses of pRGCs. Such an integration of signals enables the rods to detect dim light, the cones to detect higher light intensities and the integration of intermittent light exposure, whilst melanopsin measures bright light over extended periods of time. Although photoreceptor m...