Light effects on circadian rhythm

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Light effects on circadian rhythm are the response of circadian rhythms to light.

Contents

Most animals and other organisms have a biological clock that synchronizes their physiology and behaviour with the daily changes in the environment. The physiological changes that follow these clocks are known as circadian rhythms. Because the endogenous period of these rhythms are approximately but not exactly 24 hours, these rhythms must be reset by external cues to synchronize with the daily cycles in the environment. [1] This process is called entrainment. One of the most important cues to entrain circadian rhythms is light.

Mechanism

Light first passes into a mammal's system through the retina, then takes one of two paths: the light gets collected by rod cells and cone cells and the retinal ganglion cells (RGCs), or it is directly collected by these RGCs. [2] [3] [4] [5]

The RGCs use the photopigment melanopsin to absorb the light energy. [2] [3] [4] [5] Specifically, this class of RGCs being discussed is referred to as "intrinsically photosensitive," which just means they are sensitive to light. [2] [6] [4] There are five known types of intrinsically photosensitive retinal ganglion cells (ipRGCs): M1, M2, M3, M4, and M5. [4] Each of these differently ipRGC types have different melanopsin content and photosensitivity. [7] These connect to amacrine cells in the inner plexiform layer of the retina. [4] Ultimately, via this retinohypothalamic tract (RHT) the suprachiasmatic nucleus (SCN) of the hypothalamus receives light information from these ipRGCs. [2] [3] [4] [5]

The ipRGCs serve a different function than rods and cones, even when isolated from the other components of the retina, ipRGCs maintain their photo-sensitivity and as a result can be sensitive to different ranges of the light spectrum. [7] Additionally, ipRGC firing patterns may respond to light conditions as low as 1 lux whereas previous research indicated 2500 lux was required to suppress melatonin production. [7] Circadian and other behavioral responses have shown to be more sensitive at lower wavelengths than the photopic luminous efficiency function which is based on sensitivity to cone receptors. [7]

The core region of the SCN houses the majority of light-sensitive neurons. [8] From here, signals are transmitted via a nerve connection with the pineal gland which regulates various hormones in the human body. [9]

There are specific genes that determine the regulation of circadian rhythm in conjunction with light. [8] When light activates NMDA receptors in the SCN, CLOCK gene expression in that region is altered and the SCN is reset, and this is how entrainment occurs. [8] Genes also involved with entrainment are PER1 and PER2. [8]

Some important structures directly impacted by the light-sleep relationship are the superior colliculus-pretectal area and the ventrolateral pre-optic nucleus. [6] [5]

The progressive yellowing of the crystalline lens with age reduces the amount of short-wavelength light reaching the retina and may contribute to circadian alterations observed in older adulthood. [10]

Effects

Primary

All of the mechanisms of light-affected entrainment are not yet fully known, however numerous studies have demonstrated the effectiveness of light entrainment to the day/night cycle. Studies have shown that the timing of exposure to light influences entrainment; as seen on the phase response curve for light for a given species. In diurnal (day-active) species, exposure to light soon after wakening advances the circadian rhythm, whereas exposure before sleeping delays the rhythm. [11] [12] [8] An advance means that the individual will tend to wake up earlier on the following day(s). A delay, caused by light exposure before sleeping, means that the individual will tend to wake up later on the following day(s).

The hormones cortisol and melatonin are affected by the signals light sends through the body's nervous system. These hormones help regulate blood sugar to give the body the appropriate amount of energy that is required throughout the day. Cortisol levels are high upon waking and gradually decrease over the course of the day, melatonin levels are high when the body is entering and exiting a sleeping status and are very low over the course of waking hours. [9] The earth's natural light-dark cycle is the basis for the release of these hormones. [13]

The length of light exposure influences entrainment. Longer exposures have a greater effect than shorter exposures. [12] Consistent light exposure has a greater effect than intermittent exposure. [14] In rats, constant light eventually disrupts the cycle to the point that memory and stress coping may be impaired. [15]

The intensity and the wavelength of light influence entrainment. [2] Dim light can affect entrainment relative to darkness. [16] Brighter light is more effective than dim light. [12] In humans, a lower intensity short wavelength (blue/violet) light appears to be equally effective as a higher intensity of white light. [11]

Exposure to monochromatic light at the wavelengths of 460 nm and 550 nm on two control groups yielded results showing decreased sleepiness at 460 nm tested over two groups and a control group. Additionally, in the same study but testing thermoregulation and heart rate researchers found significantly increased heart rate in 460 nm light over the course of a 1.5 hour exposure period. [17]

In a study done on the effect of lighting intensity on delta waves, a measure of sleepiness, high levels of lighting (1700 lux) showed lower levels of delta waves measured through an EEG than low levels of lighting (450 lux). This shows that lighting intensity is directly correlated with alertness in an office environment. [18]

Humans are sensitive to light with a short wavelength. Specifically, melanopsin is sensitive to blue light with a wavelength of approximately 480 nanometers. [19] The effect this wavelength of light has on melanopsin leads to physiological responses such as the suppression of melatonin production, increased alertness, and alterations to the circadian rhythm. [19]

Secondary

While light has direct effects on circadian rhythm, there are indirect effects seen across studies. [4] Seasonal affective disorder creates a model in which decreased day length during autumn and winter increases depressive symptoms. [6] [4] A shift in the circadian phase response curve creates a connection between the amount of light in a day (day length) and depressive symptoms in this disorder. [6] [4] Light seems to have therapeutic antidepressant effects when an organism is exposed to it at appropriate times during the circadian rhythm, regulating the sleep-wake cycle. [6] [4]

In addition to mood, learning and memory become impaired when the circadian system shifts due to light stimuli, [6] [20] which can be seen in studies modeling jet lag and shift work situations. [4] Frontal and parietal lobe areas involved in working memory have been implicated in melanopsin responses to light information. [20]

"In 2007, the International Agency for Research on Cancer classified shift work with circadian disruption or chronodisruption as a probable human carcinogen." [21]

Exposure to light during the hours of melatonin production reduces melatonin production. Melatonin has been shown to mitigate the growth of tumors in rats. By suppressing the production of melatonin over the course of the night rats showed increased rates of tumors over the course of a four-week period. [22]

Artificial light at night causing circadian disruption additionally impacts sex steroid production. Increased levels of progestogens and androgens was found in night shift workers as compared to "working hour" workers. [21]

The proper exposure to light has become an accepted way to alleviate some of the effects of seasonal affective disorder (SAD). In addition exposure to light in the morning has been shown to assist Alzheimer patients in regulating their waking patterns. [23]

In response to light exposure, alertness levels can increase as a result of suppression of melatonin secretion. [3] [6] A linear relationship has been found between alerting effects of light and activation in the posterior hypothalamus. [3] [24]

Disruption of circadian rhythm as a result of light also produces changes in metabolism. [4]

Measured lighting for rating systems

Historically light was measured in the units of luminous intensity (candelas), luminance (candelas/m2) and illuminance (lumen/m2). After the discovery of ipRGCs in 2002 additional units of light measurement have been researched in order to better estimate the impact of different inputs of the spectrum of light on various photoreceptors. However, due to the variability in sensitivity between rods, cones and ipRGCs and variability between the different ipRGC types a singular unit does not perfectly reflect the effects of light on the human body. [7]

The accepted current unit is equivalent melanopic lux which is a calculated ratio multiplied by the unit lux. The melanopic ratio is determined taking into account the source type of light and the melanopic illuminance values for the eye's photopigments. [25] The source of light, the unit used to measure illuminance and the value of illuminance informs the spectral power distribution. This is used to calculate the Photopic illuminance and the melanopic lux for the five photopigments of the human eye, which is weighted based on the optical density of each photopigment. [25]

The WELL Building standard was designed for "advancing health and well-being in buildings globally" [26] Part of the standard is the implementation of Credit 54: Circadian Lighting Design. Specific thresholds for different office areas are designated in order to achieve credits. Light is measured at 1.2 meters above the finished floor for all areas.

Work areas must have at least a value of 200 equivalent melanopic lux present for 75% or more work stations between the hours of 9:00 A.M. and 1:00 P.M. for each day of the year when daylight is incorporated into calculations. If daylight is not taken into account all workstations require lighting at the value of 150 equivalent melanopic lux or greater. [27]

Living environments, which are bedrooms, bathrooms and rooms with windows, at least one fixture must provide a melanopic lux value of at least 200 during the day and a melanopic lux value less than 50 during the night, measured .76 meters above the finished floor. [27]

Breakrooms require an average melanopic lux of 250. [27]

Learning areas require either that light models which may incorporate daylighting have an equivalent melanopic lux of 125 at at least 75% of desks for at least four hours per day or ambient lights maintain the standard lux recommendations set forth by Table 3 of the IES-ANSI RP-3-13. [27]

The WELL Building standard additionally provides direction for circadian emulation in multi-family residences. In order to more accurately replicate natural cycles lighting users must be able to set a wake and bed time. An equivalent melanopic lux of 250 must be maintained in the period of the day between the indicated wake time and two hours before the indicated bed time. An equivalent melanopic lux of 50 or less is required for the period of the day spanning from two hours before the indicated bed time through the wake time. In addition at the indicated wake time melanopic lux should increase from 0 to 250 over the course of at least 15 minutes. [28]

Other factors

Although many researchers consider light to be the strongest cue for entrainment, it is not the only factor acting on circadian rhythms. Other factors may enhance or decrease the effectiveness of entrainment. For instance, exercise and other physical activity, when coupled with light exposure, results in a somewhat stronger entrainment response. [14] Other factors such as music and properly timed administration of the neurohormone melatonin have shown similar effects. [29] [30] Numerous other factors affect entrainment as well. These include feeding schedules, temperature, pharmacology, locomotor stimuli, social interaction, sexual stimuli and stress. [31]

Circadian-based effects have also been found on visual perception to discomfort glare. [32] The time of day is which people are shown a light source that produces visual discomfort is not perceived evenly. As the day progress, people tend to become more tolerant to the same levels of discomfort glare (i.e., people are more sensitive to discomfort glare in the morning compared to later in the day.) Further studies on chronotype show that early chronotypes can also tolerate more discomfort glare in the morning compared to late chronotypes. [33]

See also

Related Research Articles

Free-running sleep is a rare sleep pattern whereby the sleep schedule of a person shifts later every day. It occurs as the sleep disorder non-24-hour sleep–wake disorder or artificially as part of experiments used in the study of circadian and other rhythms in biology. Study subjects are shielded from all time cues, often by a constant light protocol, by a constant dark protocol or by the use of light/dark conditions to which the organism cannot entrain such as the ultrashort protocol of one hour dark and two hours light. Also, limited amounts of food may be made available at short intervals so as to avoid entrainment to mealtimes. Subjects are thus forced to live by their internal circadian "clocks".

<span class="mw-page-title-main">Circadian rhythm</span> Natural internal process that regulates the sleep-wake cycle

A circadian rhythm, or circadian cycle, is a natural oscillation that repeats roughly every 24 hours. Circadian rhythms can refer to any process that originates within an organism and responds to the environment. Circadian rhythms are regulated by a circadian clock whose primary function is to rhythmically co-ordinate biological processes so they occur at the correct time to maximize the fitness of an individual. Circadian rhythms have been widely observed in animals, plants, fungi and cyanobacteria and there is evidence that they evolved independently in each of these kingdoms of life.

<span class="mw-page-title-main">Chronobiology</span> Field of biology

Chronobiology is a field of biology that examines timing processes, including periodic (cyclic) phenomena in living organisms, such as their adaptation to solar- and lunar-related rhythms. These cycles are known as biological rhythms. Chronobiology comes from the ancient Greek χρόνος, and biology, which pertains to the study, or science, of life. The related terms chronomics and chronome have been used in some cases to describe either the molecular mechanisms involved in chronobiological phenomena or the more quantitative aspects of chronobiology, particularly where comparison of cycles between organisms is required.

<span class="mw-page-title-main">Delayed sleep phase disorder</span> Chronic sleep disorder

Delayed sleep phase disorder (DSPD), more often known as delayed sleep phase syndrome and also as delayed sleep–wake phase disorder, is the delaying of a person's circadian rhythm compared to those of societal norms. The disorder affects the timing of biological rhythms including sleep, peak period of alertness, core body temperature, and hormonal cycles.

<span class="mw-page-title-main">Melanopsin</span> Mammalian protein found in Homo sapiens

Melanopsin is a type of photopigment belonging to a larger family of light-sensitive retinal proteins called opsins and encoded by the gene Opn4. In the mammalian retina, there are two additional categories of opsins, both involved in the formation of visual images: rhodopsin and photopsin in the rod and cone photoreceptor cells, respectively.

Non-24-hour sleep–wake disorder is one of several chronic circadian rhythm sleep disorders (CRSDs). It is defined as a "chronic steady pattern comprising [...] daily delays in sleep onset and wake times in an individual living in a society". Symptoms result when the non-entrained (free-running) endogenous circadian rhythm drifts out of alignment with the light–dark cycle in nature. Although this sleep disorder is more common in blind people, affecting up to 70% of the totally blind, it can also affect sighted people. Non-24 may also be comorbid with bipolar disorder, depression, and traumatic brain injury. The American Academy of Sleep Medicine (AASM) has provided CRSD guidelines since 2007 with the latest update released in 2015.

A phase response curve (PRC) illustrates the transient change in the cycle period of an oscillation induced by a perturbation as a function of the phase at which it is received. PRCs are used in various fields; examples of biological oscillations are the heartbeat, circadian rhythms, and the regular, repetitive firing observed in some neurons in the absence of noise.

Intrinsically photosensitive retinal ganglion cells (ipRGCs), also called photosensitive retinal ganglion cells (pRGC), or melanopsin-containing retinal ganglion cells (mRGCs), are a type of neuron in the retina of the mammalian eye. The presence of an additional photoreceptor was first suspected in 1927 when mice lacking rods and cones still responded to changing light levels through pupil constriction; this suggested that rods and cones are not the only light-sensitive tissue. However, it was unclear whether this light sensitivity arose from an additional retinal photoreceptor or elsewhere in the body. Recent research has shown that these retinal ganglion cells, unlike other retinal ganglion cells, are intrinsically photosensitive due to the presence of melanopsin, a light-sensitive protein. Therefore, they constitute a third class of photoreceptors, in addition to rod and cone cells.

<span class="mw-page-title-main">Biological effects of high-energy visible light</span> Blue-light toxicity

High-energy visible light is short-wave light in the violet/blue band from 400 to 450 nm in the visible spectrum, which has a number of purported negative biological effects, namely on circadian rhythm and retinal health, which can lead to age-related macular degeneration. Increasingly, blue blocking filters are being designed into glasses to avoid blue light's purported negative effects. However, there is no good evidence that filtering blue light with spectacles has any effect on eye health, eye strain, sleep quality or vision quality.

Circadian rhythm sleep disorders (CRSD), also known as circadian rhythm sleep-wake disorders (CRSWD), are a family of sleep disorders which affect the timing of sleep. CRSDs arise from a persistent pattern of sleep/wake disturbances that can be caused either by dysfunction in one's biological clock system, or by misalignment between one's endogenous oscillator and externally imposed cues. As a result of this mismatch, those affected by circadian rhythm sleep disorders have a tendency to fall asleep at unconventional time points in the day. These occurrences often lead to recurring instances of disturbed rest, where individuals affected by the disorder are unable to go to sleep and awaken at "normal" times for work, school, and other social obligations. Delayed sleep phase disorder, advanced sleep phase disorder, non-24-hour sleep–wake disorder and irregular sleep–wake rhythm disorder represents the four main types of CRSD.

<span class="mw-page-title-main">Retinohypothalamic tract</span> Neural pathway involved with circadian rhythms

In neuroanatomy, the retinohypothalamic tract (RHT) is a photic neural input pathway involved in the circadian rhythms of mammals. The origin of the retinohypothalamic tract is the intrinsically photosensitive retinal ganglion cells (ipRGC), which contain the photopigment melanopsin. The axons of the ipRGCs belonging to the retinohypothalamic tract project directly, monosynaptically, to the suprachiasmatic nuclei (SCN) via the optic nerve and the optic chiasm. The suprachiasmatic nuclei receive and interpret information on environmental light, dark and day length, important in the entrainment of the "body clock". They can coordinate peripheral "clocks" and direct the pineal gland to secrete the hormone melatonin.

Ignacio Provencio is an American neuroscientist and the discoverer of melanopsin, an opsin found in specialized photosensitive ganglion cells of the mammalian retina. Provencio served as the program committee chair of the Society for Research on Biological Rhythms from 2008 to 2010.

<span class="mw-page-title-main">Light in school buildings</span>

Light in school buildings traditionally is from a combination of daylight and electric light to illuminate learning spaces, hallways, cafeterias, offices and other interior areas. Light fixtures currently in use usually provide students and teachers with satisfactory visual performance, i.e., the ability to read a book, have lunch, or play basketball in a gymnasium. However, classroom lighting may also affect students' circadian systems, which may in turn affect test scores, attendance and behavior.

Designing lighting for the elderly requires special consideration and care from architects and lighting designers. As people age, they experience neurodegeneration in the retina and in the suprachiasmatic nucleus (SCN). Less light reaches the back of the eyes because the pupils decrease in size as one ages, the lens inside one's eye becomes thicker, and the lens scatters more light, causing objects and colors to appear less vivid. These symptoms are particularly common with persons having alzheimer's disease. Older people also have reduced levels of retinal illuminance, such as having smaller pupils and less transparent crystalline lenses. Furthermore, as an individual ages, they begins to lose retinal neurons, which not only compromises the ability to see but also to register a robust daily pattern of light-dark that is needed to maintain biological rhythms. The 24-hour light-dark cycle is the most important external stimulus for regulating the timing of the circadian cycle.

<span class="mw-page-title-main">Charles Czeisler</span> American physician and sleep researcher

Charles Andrew Czeisler is a Hungarian-American physician and sleep and circadian researcher. He is a leading researcher and author in the fields of the effects of light on human physiology, circadian rhythms and sleep medicine.

Samer Hattar is a chronobiologist and a leader in the field of non-image forming photoreception. He is the Chief of the Section on Light and Circadian Rhythms at the National Institute of Mental Health, part of the National Institutes of Health. He was previously an associate professor in the Department of Neuroscience and the Department of Biology at Johns Hopkins University in Baltimore, MD. He is best known for his investigation into the role of melanopsin and intrinsically photosensitive retinal ganglion cells (ipRGC) in the entrainment of circadian rhythms.

Dr. Debra J. Skene is a chronobiologist with specific interest in the mammalian circadian rhythm and the consequences of disturbing the circadian system. She is also interested in finding their potential treatments for people who suffer from circadian misalignment. Skene and her team of researchers tackle these questions using animal models, clinical trials, and most recently, liquid chromatography-mass spectrometry. Most notably, Skene is credited for her evidence of a novel photopigment in humans, later discovered to be melanopsin. She was also involved in discovering links between human PER3 genotype and an extremely shifted sleep schedules categorized as extreme diurnal preference. Skene received her Bachelor of Pharmacy, Master of Science, and Ph.D. in South Africa.

In chronobiology, photoentrainment refers to the process by which an organism's biological clock, or circadian rhythm, synchronizes to daily cycles of light and dark in the environment. The mechanisms of photoentrainment differ from organism to organism. Photoentrainment plays a major role in maintaining proper timing of physiological processes and coordinating behavior within the natural environment. Studying organisms’ different photoentrainment mechanisms sheds light on how organisms may adapt to anthropogenic changes to the environment.

Elizabeth Klerman is a professor of neurology at Harvard Medical School. Her research focuses on applying circadian and sleep research principles to human physiology and pathophysiology. She also uses mathematical analysis and modeling to study human circadian, sleep, and objective neurobehavioral performance and subjective (self-reported) mood and alertness rhythms.

The blue light spectrum, characterized by wavelengths between 400 and 500 nanometers, has a broad impact on human health, influencing numerous physiological processes in the human body. Although blue light is essential for regulating circadian rhythms, improving alertness, and supporting cognitive function, its widespread presence has raised worries about its possible effects on general well-being.

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