Measuring and using light in the melanopsin age
University of Manchester1, University of Oxford2, Brown University3, French Institute of Health and Medical Research4, Brigham and Women's Hospital5, Rensselaer Polytechnic Institute6, University of Alabama at Birmingham7, Public Health England8, University of Virginia9, University of Surrey10, Thomas Jefferson University11
TL;DR: A new light-measurement strategy taking account of the complex photoreceptive inputs to these non-visual responses is proposed for use by researchers, and simple suggestions for artificial/architectural lighting are provided for regulatory authorities, lighting manufacturers, designers, and engineers.
About: This article is published in Trends in Neurosciences.The article was published on 2014-01-01 and is currently open access. It has received 886 citations till now. The article focuses on the topics: Melanopsin & Intrinsically photosensitive retinal ganglion cells.
Citations
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TL;DR: It is found that the use of portable light-emitting devices immediately before bedtime has biological effects that may perpetuate sleep deficiency and disrupt circadian rhythms, both of which can have adverse impacts on performance, health, and safety.
Abstract: In the past 50 y, there has been a decline in average sleep duration and quality, with adverse consequences on general health. A representative survey of 1,508 American adults recently revealed that 90% of Americans used some type of electronics at least a few nights per week within 1 h before bedtime. Mounting evidence from countries around the world shows the negative impact of such technology use on sleep. This negative impact on sleep may be due to the short-wavelength–enriched light emitted by these electronic devices, given that artificial-light exposure has been shown experimentally to produce alerting effects, suppress melatonin, and phase-shift the biological clock. A few reports have shown that these devices suppress melatonin levels, but little is known about the effects on circadian phase or the following sleep episode, exposing a substantial gap in our knowledge of how this increasingly popular technology affects sleep. Here we compare the biological effects of reading an electronic book on a light-emitting device (LE-eBook) with reading a printed book in the hours before bedtime. Participants reading an LE-eBook took longer to fall asleep and had reduced evening sleepiness, reduced melatonin secretion, later timing of their circadian clock, and reduced nextmorning alertness than when reading a printed book. These results demonstrate that evening exposure to an LE-eBook phase-delays the circadian clock, acutely suppresses melatonin, and has important implications for understanding the impact of such technologies on sleep, performance, health, and safety.
836 citations
Cites background or methods from "Measuring and using light in the me..."
...In humans, exposure to short-wavelength monochromatic light in the evening has been shown to induce greater circadian and alerting responses than exposure to the same number of photons of longer-wavelength monochromatic light (17–19, 28–34), even though the shorter-wavelength light may have a much lower illuminance level when measured in photopic lux (35)....
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...The irradiance output in the range of 380–780 nm at 4-nm intervals was converted to 1-nm intervals for calculation of the human retinal photopigment illuminance measures (cyanopic, melanopic, rhodopic, chloropic, and erythropic lux) (35)....
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...For this reason, it has recently been proposed that lux is an inappropriate measure for estimation of the impact of light on melatonin suppression, circadian-phase shifting, and other non–imageforming effects of retinal light exposure (35)....
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TL;DR: Melatonin is a small, highly conserved indole with numerous receptor-mediated and receptor-independent actions that relate to melatonin's ability to function in the detoxification of free radicals, thereby protecting critical molecules from the destructive effects of oxidative stress under conditions of ischemia/reperfusion injury, ionizing radiation, and drug toxicity.
Abstract: Melatonin is a small, highly conserved indole with numerous receptor-mediated and receptor-independent actions. Receptor-dependent functions include circadian rhythm regulation, sleep, and cancer inhibition. The receptor-independent actions relate to melatonin's ability to function in the detoxification of free radicals, thereby protecting critical molecules from the destructive effects of oxidative stress under conditions of ischemia/reperfusion injury (stroke, heart attack), ionizing radiation, and drug toxicity, among others. Melatonin has numerous applications in physiology and medicine.
431 citations
Cites background from "Measuring and using light in the me..."
...For the retinal processing of blue wavelengths, the mammalian retinas have up to five highly specialized subtypes of intrinsically photosensitive retinal ganglion cells (ipRGCs), which use a specialized photopigment, melanopsin, to respond to light (31, 68)....
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TL;DR: Timed meals play a role in synchronizing peripheral circadian rhythms in humans and may have particular relevance for patients with circadian rhythm disorders, shift workers, and transmeridian travelers.
322 citations
Cites background from "Measuring and using light in the me..."
...In most individuals, the SCN clock is set to solar time by photic input pathways originating in the retina [6]; the SCN then synchronize peripheral clocks through neuronal pathways, hormone rhythms, core body temperature, and behaviors such as the cycle of feeding and fasting [3]....
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Journal Article•
TL;DR: This review summarizes the current knowledge of the effects of blue light on the regulation of physiologic functions and the possible effects ofblue light exposure on ocular health and the spectral output of LED-based light sources to minimize the danger that may be associated with blue light exposure.
Abstract: Light-emitting diodes (LEDs) have been used to provide illumination in industrial and commercial environments. LEDs are also used in TVs, computers, smart phones, and tablets. Although the light emitted by most LEDs appears white, LEDs have peak emission in the blue light range (400-490 nm). The accumulating experimental evidence has indicated that exposure to blue light can affect many physiologic functions, and it can be used to treat circadian and sleep dysfunctions. However, blue light can also induce photoreceptor damage. Thus, it is important to consider the spectral output of LED-based light sources to minimize the danger that may be associated with blue light exposure. In this review, we summarize the current knowledge of the effects of blue light on the regulation of physiologic functions and the possible effects of blue light exposure on ocular health.
317 citations
Cites background from "Measuring and using light in the me..."
...Thus, the current view is that no single photoreceptor type is necessary for the synchronization of circadian rhythms with external light-dark cycles [30,31]....
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National Institutes of Health1, Tulane University2, Maynooth University3, Rensselaer Polytechnic Institute4, University of California, San Diego5, The Ohio State University Wexner Medical Center6, Salk Institute for Biological Studies7, University of Texas at Austin8, University of Connecticut9, Northwestern University10, Utrecht University11, National Institute for Occupational Safety and Health12, Durham University13
TL;DR: An expert panel suggested describing light both as a direct effector of endogenous circadian clocks and rhythms and as an enabler of additional activities or behaviors that may lead to circadian disruption, such as night-shift work and atypical and inconsistent sleep-wake patterns that can lead to social jet lag.
235 citations
Cites background or methods from "Measuring and using light in the me..."
...Using these data, two spectral sensitivity functions and one mathematical model have been proposed and published in peer-reviewed journals, as described by Lucas et al. (2014)....
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...It is also important that researchers start reporting the light stimulus used in their studies in a more uniform manner, as proposed by Lucas et al. (2014)....
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References
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TL;DR: It is shown that retinal ganglion cells innervating the SCN are intrinsically photosensitive, and depolarized in response to light even when all synaptic input from rods and cones was blocked.
Abstract: Light synchronizes mammalian circadian rhythms with environmental time by modulating retinal input to the circadian pacemaker-the suprachiasmatic nucleus (SCN) of the hypothalamus. Such photic entrainment requires neither rods nor cones, the only known retinal photoreceptors. Here, we show that retinal ganglion cells innervating the SCN are intrinsically photosensitive. Unlike other ganglion cells, they depolarized in response to light even when all synaptic input from rods and cones was blocked. The sensitivity, spectral tuning, and slow kinetics of this light response matched those of the photic entrainment mechanism, suggesting that these ganglion cells may be the primary photoreceptors for this system.
3,052 citations
TL;DR: It is shown that melanopsin is present in cell bodies, dendrites, and proximal axonal segments of a subset of rat RGCs, most likely the visual pigment of phototransducing R GCs that set the circadian clock and initiate other non–image-forming visual functions.
Abstract: The primary circadian pacemaker, in the suprachiasmatic nucleus (SCN) of the mammalian brain, is photoentrained by light signals from the eyes through the retinohypothalamic tract. Retinal rod and cone cells are not required for photoentrainment. Recent evidence suggests that the entraining photoreceptors are retinal ganglion cells (RGCs) that project to the SCN. The visual pigment for this photoreceptor may be melanopsin, an opsin-like protein whose coding messenger RNA is found in a subset of mammalian RGCs. By cloning rat melanopsin and generating specific antibodies, we show that melanopsin is present in cell bodies, dendrites, and proximal axonal segments of a subset of rat RGCs. In mice heterozygous for tau-lacZ targeted to the melanopsin gene locus, beta-galactosidase-positive RGC axons projected to the SCN and other brain nuclei involved in circadian photoentrainment or the pupillary light reflex. Rat RGCs that exhibited intrinsic photosensitivity invariably expressed melanopsin. Hence, melanopsin is most likely the visual pigment of phototransducing RGCs that set the circadian clock and initiate other non-image-forming visual functions.
2,359 citations
TL;DR: Findings establish that the human response to light is qualitatively similar to that of other mammals.
Abstract: Bright artificial light suppressed nocturnal secretion of melatonin in six normal human subjects. Room light of less intensity, which is sufficient to suppress melatonin secretion in other mammals, failed to do so in humans. In contrast to the results of previous experiments in which ordinary room light was used, these findings establish that the human response to light is qualitatively similar to that of other mammals.
1,776 citations
TL;DR: The results suggest that, in humans, a single photopigment may be primarily responsible for melatonin suppression, and its peak absorbance appears to be distinct from that of rod and cone cellphotopigments for vision.
Abstract: The photopigment in the human eye that transduces light for circadian and neuroendocrine regulation, is unknown. The aim of this study was to establish an action spectrum for light-induced melatonin suppression that could help elucidate the ocular photoreceptor system for regulating the human pineal gland. Subjects (37 females, 35 males, mean age of 24.5 +/- 0.3 years) were healthy and had normal color vision. Full-field, monochromatic light exposures took place between 2:00 and 3:30 A.M. while subjects' pupils were dilated. Blood samples collected before and after light exposures were quantified for melatonin. Each subject was tested with at least seven different irradiances of one wavelength with a minimum of 1 week between each nighttime exposure. Nighttime melatonin suppression tests (n = 627) were completed with wavelengths from 420 to 600 nm. The data were fit to eight univariant, sigmoidal fluence-response curves (R(2) = 0.81-0.95). The action spectrum constructed from these data fit an opsin template (R(2) = 0.91), which identifies 446-477 nm as the most potent wavelength region providing circadian input for regulating melatonin secretion. The results suggest that, in humans, a single photopigment may be primarily responsible for melatonin suppression, and its peak absorbance appears to be distinct from that of rod and cone cell photopigments for vision. The data also suggest that this new photopigment is retinaldehyde based. These findings suggest that there is a novel opsin photopigment in the human eye that mediates circadian photoreception.
1,708 citations
TL;DR: The data strongly support a primary role for a novel short‐wavelength photopigment in light‐induced melatonin suppression and provide the first direct evidence of a non‐rod, non‐cone photoreceptive system in humans.
Abstract: 1 Non-image forming, irradiance-dependent responses mediated by the human eye include synchronisation of the circadian axis and suppression of pineal melatonin production The retinal photopigment(s) transducing these light responses in humans have not been characterised 2 Using the ability of light to suppress nocturnal melatonin production, we aimed to investigate its spectral sensitivity and produce an action spectrum Melatonin suppression was quantified in 22 volunteers in 215 light exposure trials using monochromatic light (30 min pulse administered at circadian time (CT) 16-18) of different wavelengths (lambda(max) 424, 456, 472, 496, 520 and 548 nm) and irradiances (07-650 microW cm(-2)) 3 At each wavelength, suppression of plasma melatonin increased with increasing irradiance Irradiance-response curves (IRCs) were fitted and the generated half-maximal responses (IR(50)) were corrected for lens filtering and used to construct an action spectrum 4 The resulting action spectrum showed unique short-wavelength sensitivity very different from the classical scotopic and photopic visual systems The lack of fit (r(2) or =073) Of these, the best fit was to the rhodopsin template with lambda(max) 459 nm (r(2) = 074) 5 Our data strongly support a primary role for a novel short-wavelength photopigment in light-induced melatonin suppression and provide the first direct evidence of a non-rod, non-cone photoreceptive system in humans
1,232 citations