scholarly journals High Sensitivity of the Human Circadian Melatonin Rhythm to Resetting by Short Wavelength Light

2003 ◽  
Vol 88 (9) ◽  
pp. 4502-4505 ◽  
Author(s):  
Steven W. Lockley ◽  
George C. Brainard ◽  
Charles A. Czeisler
Keyword(s):  
Ganglion Cells ◽  
Light Exposure ◽  
Monochromatic Light ◽  
High Sensitivity ◽  
Photon Density ◽  
Retinal Ganglion ◽  
Circadian Pacemaker ◽  
Melatonin Rhythm ◽  
Circadian Phase ◽  
Short Wavelength Light

The endogenous circadian oscillator in mammals, situated in the suprachiasmatic nuclei, receives environmental photic input from specialized subsets of photoreceptive retinal ganglion cells. The human circadian pacemaker is exquisitely sensitive to ocular light exposure, even in some people who are otherwise totally blind. The magnitude of the resetting response to white light depends on the timing, intensity, duration, number and pattern of exposures. We report here that the circadian resetting response in humans, as measured by the pineal melatonin rhythm, is also wavelength dependent. Exposure to 6.5 h of monochromatic light at 460 nm induces a two-fold greater circadian phase delay than 6.5 h of 555 nm monochromatic light of equal photon density. Similarly, 460 nm monochromatic light causes twice the amount of melatonin suppression compared to 555 nm monochromatic light, and is dependent on the duration of exposure in addition to wavelength. These studies demonstrate that the peak of sensitivity of the human circadian pacemaker to light is blue-shifted relative to the three-cone visual photopic system, the sensitivity of which peaks at ∼555 nm. Thus photopic lux, the standard unit of illuminance, is inappropriate when quantifying the photic drive required to reset the human circadian pacemaker.

scholarly journals Fundamentals of circadian entrainment by light

2021 ◽  
Vol 53 (5) ◽  
pp. 377-393
Author(s):  
RG Foster
Keyword(s):  
Ganglion Cells ◽  
Light Exposure ◽  
Bright Light ◽  
Evidence Based ◽  
Retinal Ganglion ◽  
Rods And Cones ◽  
Long Duration ◽  
Lighting Systems ◽  
Short Wavelength Light ◽  
Wavelength Light

Light at dawn and dusk is the key signal for the entrainment of the circadian clock. Light at dusk delays the clock. Light at dawn advances the clock. The threshold for human entrainment requires relatively bright light for a long duration, but the precise irradiance/duration relationships for photoentrainment have yet to be fully defined. Photoentrainment is achieved by a network of photosensitive retinal ganglion cells (pRGCs) which utilise the short-wavelength light-sensitive photopigment, melanopsin. Although rods and cones are not required, they do play a role in photoentrainment, by projecting to and modulating the endogenous photosensitivity of the pRGCs, but in a manner that remains poorly understood. It is also important to emphasise that the age and prior light exposure of an individual will modify the efficacy of entrainment stimuli. Because of the complexity of photoreceptor interactions, attempts to develop evidence-based human centric lighting are not straightforward. We need to study how humans respond to dynamic light exposure in the ‘real world’ where light intensity, duration, spectral quality and the time of exposure vary greatly. Defining these parameters will allow the development of electric lighting systems that will enhance human circadian entrainment.

scholarly journals No evidence for an S cone contribution to the human circadian response to light

2019 ◽  
Author(s):  
Manuel Spitschan ◽  
Rafael Lazar ◽  
Ebru Yetik ◽  
Christian Cajochen
Keyword(s):  
Retinal Ganglion Cells ◽  
Short Wavelength ◽  
Ganglion Cells ◽  
Light Exposure ◽  
Retinal Ganglion ◽  
Long Wavelength ◽  
Short Wavelength Light ◽  
The Brain ◽  
Wavelength Light

Exposure to even moderately bright, short-wavelength light in the evening can strongly suppress the production of melatonin and can delay our circadian rhythm. These effects are mediated by the retinohypothalamic pathway, connecting a subset of retinal ganglion cells to the circadian pacemaker in the suprachiasmatic nucleus (SCN) in the brain. These retinal ganglion cells directly express the photosensitive protein melanopsin, rendering them intrinsically photosensitive (ipRGCs). But ipRGCs also receive input from the classical photoreceptors — the cones and rods. Here, we examined whether the short-wavelength-sensitive (S) cones contribute to circadian photoreception by using lights which differed exclusively in the amount of S cone excitation by almost two orders of magnitude (ratio 1:83), but not in the excitation of long-wavelength-sensitive (L) and medium-wavelength-sensitive (M) cones, rods, and melanopsin. We find no evidence for a role of S cones in the acute alerting and melatonin supressing response to evening light exposure, pointing to an exclusive role of melanopsin in driving circadian responses.

scholarly journals Rest-activity cycles and melatonin phase angle of circadian entrainment in people without cone-mediated vision

2020 ◽  
Author(s):  
Manuel Spitschan ◽  
Corrado Garbazza ◽  
Susanne Kohl ◽  
Christian Cajochen
Keyword(s):  
Ganglion Cells ◽  
Light Exposure ◽  
Activity Patterns ◽  
External World ◽  
Circadian Phase ◽  
Cone System ◽  
Retinohypothalamic Tract ◽  
Activity Cycles ◽  
Phase Angles ◽  
Rest Activity

AbstractLight is strong zeitgeber to the human circadian system, entraining internal rhythms in physiology and behaviour to the external world. This is mediated by the melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs), which sense light in addition to the classical photoreceptors, the cones and rods. Circadian responses depend on light intensity, with exposure to brighter light leading to bigger circadian phase shifts and melatonin suppression. In congenital achromatopsia (prevalence 1 in 30,000 to 50,000 people), the cone system is non-functional, resulting in light avoidance and photophobia at light levels which are tolerable and habitual to individuals with a normal, trichromatic retina. Here, we examined chronotype and self-reported sleep, actigraphy-derived rest-activity cycles and increases melatonin in the evening in a group of genetically confirmed congenital achromats. We found normal rest-activity patterns in all participants, and normal melatonin phase angles of entrainment in 2/3 of our participants. Our results suggest that a functional cone system and exposure to daytime light intensities are not necessary for regular behavioural and hormonal entrainment. This may point to a compensation mechanism in circadian photoreception, which in conjunction with non-photic zeitgebers, ensures synchronisation of activity to the external world.Significance statementRhythms in physiology and behaviour are synchronised to the external cycle of light exposure. This is mediated by the retinohypothalamic tract, which connects the photoreceptors in the eye with the “circadian pacemaker” in our brain, the suprachiasmatic nucleus. What happens to our circadian rhythm when we lack the cone photoreceptors in the eye that enable us to see in daylight? We examined this question in a group of rare congenital achromats. Our work reveals that normal rhythms in rest and activity, and production of hormones, does not require a functional cone system.

Controlling the number of melanopsin-containing retinal ganglion cells by early light exposure

2013 ◽  
Vol 111 ◽  
pp. 17-26 ◽  
Author(s):  
Jie Hong ◽  
Qiang Zeng ◽  
Huaizhou Wang ◽  
Debbie S. Kuo ◽  
William H. Baldridge ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Light Exposure ◽  
Retinal Ganglion

scholarly journals Architecture of retinal projections to the central circadian pacemaker

2016 ◽  
Vol 113 (21) ◽  
pp. 6047-6052 ◽  
Author(s):  
Diego Carlos Fernandez ◽  
Yi-Ting Chang ◽  
Samer Hattar ◽  
Shih-Kuo Chen
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Microscopic Analysis ◽  
Brain Regions ◽  
Retinal Ganglion ◽  
Circadian Pacemaker ◽  
Retinal Neurons ◽  
Retinal Input ◽  
Innervation Patterns ◽  
Left And Right

The suprachiasmatic nucleus (SCN) receives direct retinal input from the intrinsically photosensitive retinal ganglion cells (ipRGCs) for circadian photoentrainment. Interestingly, the SCN is the only brain region that receives equal inputs from the left and right eyes. Despite morphological assessments showing that axonal fibers originating from ipRGCs cover the entire SCN, physiological evidence suggests that only vasoactive intestinal polypeptide (VIP)/gastrin-releasing peptide (GRP) cells located ventrally in the SCN receive retinal input. It is still unclear, therefore, which subpopulation of SCN neurons receives synaptic input from the retina and how the SCN receives equal inputs from both eyes. Here, using single ipRGC axonal tracing and a confocal microscopic analysis in mice, we show that ipRGCs have elaborate innervation patterns throughout the entire SCN. Unlike conventional retinal ganglion cells (RGCs) that innervate visual targets either ipsilaterally or contralaterally, a single ipRGC can bilaterally innervate the SCN. ipRGCs form synaptic contacts with major peptidergic cells of the SCN, including VIP, GRP, and arginine vasopressin (AVP) neurons, with each ipRGC innervating specific subdomains of the SCN. Furthermore, a single SCN-projecting ipRGC can send collateral inputs to many other brain regions. However, the size and complexity of the axonal arborizations in non-SCN regions are less elaborate than those in the SCN. Our results provide a better understanding of how retinal neurons connect to the central circadian pacemaker to synchronize endogenous circadian clocks with the solar day.

scholarly journals A Novel Reporter Mouse Uncovers Endogenous Brn3b Expression

2019 ◽  
Vol 20 (12) ◽  
pp. 2903 ◽  
Author(s):  
Adam M. Miltner ◽  
Yesica Mercado-Ayon ◽  
Simranjeet K. Cheema ◽  
Pengfei Zhang ◽  
Robert J. Zawadzki ◽  
...  
Keyword(s):  
Ganglion Cells ◽  
High Sensitivity ◽  
Retinal Ganglion ◽  
Fluorescent Intensity ◽  
Reporter Mouse ◽  
Neuronal Populations ◽  
Pou Domain ◽  
Endogenous Expression ◽  
Reporter Mice ◽  
The Central Nervous System

Brn3b (Pou4f2) is a class-4 POU domain transcription factor known to play central roles in the development of different neuronal populations of the Central Nervous System, including retinal ganglion cells (RGCs), the neurons that connect the retina with the visual centers of the brain. Here, we have used CRISPR-based genetic engineering to generate a Brn3b-mCherry reporter mouse without altering the endogenous expression of Brn3b. In our mouse line, mCherry faithfully recapitulates normal Brn3b expression in the retina, the optic tracts, the midbrain tectum, and the trigeminal ganglia. The high sensitivity of mCherry also revealed novel expression of Brn3b in the neuroectodermal cells of the optic stalk during early stages of eye development. Importantly, the fluorescent intensity of Brn3b-mCherry in our reporter mice allows for noninvasive live imaging of RGCs using Scanning Laser Ophthalmoscopy (SLO), providing a novel tool for longitudinal monitoring of RGCs.

256 Spectrophotometric Properties of 31 Different Commercially Available Blue Blocking Glasses Under Electric Room Lighting

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A103-A103
Author(s):  
Destiny Rupple ◽  
Brooke Mason ◽  
Andrew Tubbs ◽  
Fabian-Xosé Fernandez ◽  
Michael Grandner
Keyword(s):  
Ganglion Cells ◽  
Light Exposure ◽  
Visible Spectrum ◽  
Retinal Ganglion ◽  
Fluorescent Lamps ◽  
Wide Range ◽  
Indoor Conditions ◽  
Fluorescent Lighting ◽  
One Way Anova ◽  
Room Lighting

Abstract Introduction Blue blocking glasses are often marketed to promote relaxation, sleep, and circadian health by attenuating melatonin-suppressing light exposure. But these glasses represent a wide range of tint and other lens properties. Further, the utility of these glasses under ecologically valid indoor conditions (where light is typically generated from overhead broadspectrum fluorescent lamps) is still unclear, especially across various products. Methods A calibrated spectroradiometer (Ocean Insight), cosine corrector, optic fiber, and software package were used to measure the absolute irradiance (uW/cm^2/nm) emitted from overhead fluorescent lighting in a closeted dark room. Thirty-one commercially available blue blockers were individually placed between the cosine corrector and the luminaire, at a standardized distance and angle, where intensity was measured and analyzed. Each lens was evaluated individually relative to the light source under identical conditions. Then, lenses were collapsed by type into the following groups: red-tinted lenses (RTL), orange-tinted lenses (OTL), orange-tinted lenses with blue reflectivity (OBL), brown-tinted lenses (BTL), yellow-tinted lenses (YTL), and clear reflective blue lenses (RBL). Results There was significant variation in light-blocking across lens types (one-way ANOVA, p < 0.0001). On average, RTL and BTL restricted 59% of the visible light measured from 380-780nm. OTL blocked 47% of the light in this range, while OBL blocked 29%. Both YTL and RBL blocked 14% of the exposure. When narrowing the range of light to 440-530nm (the part of the spectrum most likely to produce a response from melanopsin-expressing retinal ganglion cells), we estimated the following performance: the RTL and OTL blocked close to 100% of the light, OBL blocked 98%, BTL blocked 80%, YTL blocked 33%, and RBL blocked 15%. These differences were statistically significant (one-way ANOVA, p < 0.0001). Individual lenses performed variably within groups, but these differences were small. Conclusion Focusing on the portion of the visible spectrum most likely to suppress melatonin secretion, RTL and OTL blocked exposure the best, followed by OBL, BTL, YTL, and (lastly) RBL. Support (if any) R01MD011600, R01DA051321

scholarly journals Dissecting and modeling photic and melanopsin effects to predict sleep disturbances induced by irregular light exposure in mice

2021 ◽  
Vol 118 (25) ◽  
pp. e2017364118
Author(s):  
Jeffrey Hubbard ◽  
Mio Kobayashi Frisk ◽  
Elisabeth Ruppert ◽  
Jessica W. Tsai ◽  
Fanny Fuchs ◽  
...  
Keyword(s):  
Sleep Disturbances ◽  
Ganglion Cells ◽  
Light Exposure ◽  
Day Length ◽  
Retinal Ganglion ◽  
Suprachiasmatic Nuclei ◽  
Artificial Lighting ◽  
Direct Light ◽  
Light Effects ◽  
Length Changes

Artificial lighting, day-length changes, shift work, and transmeridian travel all lead to sleep–wake disturbances. The nychthemeral sleep–wake cycle (SWc) is known to be controlled by output from the central circadian clock in the suprachiasmatic nuclei (SCN), which is entrained to the light–dark cycle. Additionally, via intrinsically photosensitive retinal ganglion cells containing the photopigment melanopsin (Opn4), short-term light–dark alternations exert direct and acute influences on sleep and waking. However, the extent to which longer exposures typically experienced across the 24-h day exert such an effect has never been clarified or quantified, as disentangling sustained direct light effects (SDLE) from circadian effects is difficult. Recording sleep in mice lacking a circadian pacemaker, either through transgenesis (Syt10cre/creBmal1fl/-) or SCN lesioning and/or melanopsin-based phototransduction (Opn4−/−), we uncovered, contrary to prevailing assumptions, that the contribution of SDLE is as important as circadian-driven input in determining SWc amplitude. Specifically, SDLE were primarily mediated (>80%) through melanopsin, of which half were then relayed through the SCN, revealing an ancillary purpose for this structure, independent of its clock function in organizing SWc. Based on these findings, we designed a model to estimate the effect of atypical light–dark cycles on SWc. This model predicted SWc amplitude in mice exposed to simulated transequatorial or transmeridian paradigms. Taken together, we demonstrate this SDLE is a crucial mechanism influencing behavior on par with the circadian system. In a broader context, these findings mandate considering SDLE, in addition to circadian drive, for coping with health consequences of atypical light exposure in our society.

scholarly journals Neuropsin (OPN5)-mediated photoentrainment of local circadian oscillators in mammalian retina and cornea

2015 ◽  
Vol 112 (42) ◽  
pp. 13093-13098 ◽  
Author(s):  
Ethan D. Buhr ◽  
Wendy W. S. Yue ◽  
Xiaozhi Ren ◽  
Zheng Jiang ◽  
Hsi-Wen Rock Liao ◽  
...  
Keyword(s):  
Short Wavelength ◽  
Ganglion Cells ◽  
Ex Vivo ◽  
Retinal Ganglion ◽  
Light Sensing ◽  
Cone Opsin ◽  
Circadian Oscillators ◽  
Environmental Light ◽  
Mammalian Retina ◽  
Short Wavelength Light

The molecular circadian clocks in the mammalian retina are locally synchronized by environmental light cycles independent of the suprachiasmatic nuclei (SCN) in the brain. Unexpectedly, this entrainment does not require rods, cones, or melanopsin (OPN4), possibly suggesting the involvement of another retinal photopigment. Here, we show that the ex vivo mouse retinal rhythm is most sensitive to short-wavelength light but that this photoentrainment requires neither the short-wavelength–sensitive cone pigment [S-pigment or cone opsin (OPN1SW)] nor encephalopsin (OPN3). However, retinas lacking neuropsin (OPN5) fail to photoentrain, even though other visual functions appear largely normal. Initial evidence suggests that OPN5 is expressed in select retinal ganglion cells. Remarkably, the mouse corneal circadian rhythm is also photoentrainable ex vivo, and this photoentrainment likewise requires OPN5. Our findings reveal a light-sensing function for mammalian OPN5, until now an orphan opsin.

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