Age-associated changes in the circadian rhythm of retinal N-acetylserotonin and melatonin in rats with pigmented eyes (original) (raw)
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Chronobiology International, 2016
The melanopsin system consists of intrinsically photosensitive retinal ganglion cells containing the photopigment melanopsin (mRGCs). These mRGCs mediate several non-image-forming visual functions, including light entrainment of circadian rhythms. Here we evaluate age-related alterations of the melanopsin system and circadian rhythms in P23H line 1 (P23H-1) rats, a rodent model of retinitis pigmentosa (RP). In homozygous P23H-1 rats and wild-type control rats from the same genetic background (Sprague-Dawley), body temperature and locomotor activity were continuously monitored at 10-min intervals for 7 days, once every 4-5 weeks, between 2 and 24 months of age, using a telemetry transmitter. The distribution and number of mRGCs were assessed in control rats at 12, 18, and 24 months of age and in P23H-1 rats aged 12, 18, 24, and 30 months by immunostaining whole-mount retinas with antibodies against melanopsin. The mean density of mRGCs in control rats showed no significant variations when evaluated at 12 and 18 months of age, and fell by approximately 56% between 18 and 24 months of age. Meanwhile, a significant decrease in the mean number of mRGCs was found in 18-month-old P23H-1 rats as compared to 18-month-old control rats (81% decrease). Parametric and non-parametric analyses of the records showed a gradual age-dependent weakening of body temperature and locomotor activity circadian rhythms robustness in both control and P23H-1 rats from 2 to 24 months of age. However, body temperature and locomotor activity circadian patterns were less robust throughout the experiment in P23H-1 as compared to control rats, with lower amplitude, weaker coupling strength to environmental zeitgebers and higher fragmentation of the rhythms. The present study shows that the degeneration of photoreceptors and inner retinal neurons, characteristic of RP, has age-related degenerative effects on the melanopsin system and is associated with weaker circadian patterns.
PLoS ONE, 2012
Retinal melatonin is involved in the modulation of many important retinal functions. Our previous studies have shown that the viability of photoreceptors and ganglion cells is reduced during aging in mice that lack melatonin receptor type 1. This demonstrates that melatonin signaling is important for the survival of retinal neurons. In the present study, we investigate the effects of aging on photoreceptor physiology and retinal organization in CH3-f+/+ mice, a melatonin proficient mouse strain. Our data indicate that the amplitude of the a and b waves of the scotopic and photopic electroretinogram decreases with age. Moreover, the daily rhythm in the amplitude of the a-and b-waves is lost during the aging process. Similarly, the scotopic threshold response is significantly affected by aging, but only when it is measured during the night. Interestingly, the changes observed in the ERGs are not paralleled by relevant changes in retinal morphological features, and administration of exogenous melatonin does not affect the ERGs in C3H-f +/+ at 12 months of age. This suggests that the responsiveness of the photoreceptors to exogenous melatonin is reduced during aging.
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
Melatonin suppression by light involves different retinal photoreceptors in young and older adults
bioRxiv (Cold Spring Harbor Laboratory), 2023
Introduction: Age-related sleep and circadian rhythm disturbances may be due to altered nonvisual photoreception. Here, we investigated the temporal dynamics of light-induced melatonin suppression in young and older individuals. Methods: In a within-subject design study, young and older participants were exposed for 60 minutes (0030-0130 at night) to 9 narrow-band lights (range: 420 to 620 nm). Plasma melatonin suppression was calculated at 15, 30, 45, and 60 min time intervals. Individual spectral sensitivity of melatonin suppression and photoreceptor contribution were predicted for each interval and age group. Results: In young participants, melanopsin solely drove melatonin suppression at all time intervals, with an invariant peak sensitivity at ~485 nm established only after 15 minutes of light exposure. Conversely, in older participants, spectral light-driven melatonin suppression was best explained by a model combining melanopsin + L-cones with a stable peak sensitivity (~499 nm) at 30, 45, and 60 minutes of light exposure. Conclusion: Aging is associated with a distinct photoreceptor contribution to melatonin suppression by light. While in young adults melanopsin-only photoreception is a reliable predictor of melatonin suppression, in older individuals this process is jointly driven by melanopsin and L-cones. These findings offer new prospects for customizing light therapy for older individuals.
Neuroscience Letters, 1992
Effects of light on the pineal and plasma melatonin were examined in Wistar and Long-Evans rats at two different times in the dark phase (light off from 18.00 h to 06.00 h) using lights of two different monochromatic wavelengths but with the same irradiance. The green light pulse (520 nm) given at 24.00 h suppressed the pineal and plasma melatonin to the daytime level for at least 2 h, while the red light (660 nm) pulse given at the same time of the day suppressed pineal melatonin only transiently and did not suppress the plasma melatonin at all. Both green and red lights given at 4.00 h suppressed the pineal and plasma melatonin to a similar extent. The results demonstrated that the suppression of melatonin by light depends on the wavelength of light and the circadian phase.
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...