Melanopsin and the Intrinsically Photosensitive Retinal Ganglion Cells: Biophysics to Behavior

H., Michael Tri

doi:10.1016/j.neuron.2019.07.016

Cited by 184 publications

(209 citation statements)

References 264 publications

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“…37 Overall, our study adds to the existing body of findings showing that melanopsin is primarily responsible for nonvisual effects of light. 6,10,33,40,41 The new melanopic model allows us to reproduce circadian phase resetting response to light with different spectral properties as observed in experiments. 2,33,36,38 Conversion of the model to use melanopic irradiance instead of photopic illuminance involved a change of the illuminance-based model parameters of the dynamic circadian oscillator to equivalent values in melanopic irradiance.…”

Section: Discussionmentioning

confidence: 99%

“…Melanopsin plays the key role in mediating the nonvisual effects of light, and the SCN is almost exclusively innervated by ipRGCs. 10 We focus on the melanopsin system as the primary contributor to the ipRGC-influenced responses to light but note that the more complex interactions among opsins can be present depending on light irradiance and duration. 33 The melanopic irradiance is defined as the spectral irradiance, E e, , of light weighted by the melanopsin action spectrum, S mel ( ), and is based on the CIE DIS 026/E:2018 standard definition 12 with the unit of W/m 2 .…”

Section: Calculation Of Melanopic Irradiancementioning

confidence: 99%

“…8 The short-wavelength sensitivity of the nonvisual system is due to the contribution of intrinsically photosensitive retinal ganglion cells (ipRGCs) 9 which express a photopigment, melanopsin, and project via the retinohypothalamic tract to the SCN and other brain regions. 10,11 Melanopsin-containing cells are most sensitive to shorter wavelength of light (λ max 480 nm) than the visual photopic system (λ max 555 nm), thus making the nonvisual system more sensitive to blue or blue-enriched light. To address this difference between visual and nonvisual effects of light, the melanopic measure of light was introduced to replace the conventional photopic illuminance that is used to describe visual effects due to cones.…”

Section: Introductionmentioning

confidence: 99%

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Modeling melanopsin‐mediated effects of light on circadian phase, melatonin suppression, and subjective sleepiness

Tekieh

Lockley

Robinson

et al. 2020

Journal of Pineal Research

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A physiologically based model of arousal dynamics is improved to incorporate the effects of the light spectrum on circadian phase resetting, melatonin suppression, and subjective sleepiness. To account for these nonvisual effects of light, melanopic irradiance replaces photopic illuminance that was used previously in the model. The dynamic circadian oscillator is revised according to the melanopic irradiance definition and tested against experimental circadian phase resetting dose‐response and phase response data. Melatonin suppression function is recalibrated against melatonin dose‐response data for monochromatic and polychromatic light sources. A new light‐dependent term is introduced into the homeostatic weight component of subjective sleepiness to represent the direct alerting effect of light; the new term responds to light change in a time‐dependent manner and is calibrated against experimental data. The model predictions are compared to a total of 14 experimental studies containing 26 data sets for 14 different spectral light profiles. The revised melanopic model shows on average 1.4 times lower prediction error for circadian phase resetting compared to the photopic‐based model, 3.2 times lower error for melatonin suppression, and 2.1 times lower error for subjective sleepiness. Overall, incorporating melanopic irradiance allowed simulation of wavelength‐dependent responses to light and could explain the majority of the observations. Moving forward, models of circadian phase resetting and the direct effects of light on alertness and sleep need to use nonvisual photoreception‐based measures of light, for example, melanopic irradiance, instead of the traditionally used illuminance based on the visual system.

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Section: Discussionmentioning

confidence: 99%

Section: Calculation Of Melanopic Irradiancementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Modeling melanopsin‐mediated effects of light on circadian phase, melatonin suppression, and subjective sleepiness

Tekieh

Lockley

Robinson

et al. 2020

Journal of Pineal Research

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“…Light emerging from human affairs distorts bird reproductive behavior and mating patterns [111]. Melanopsin, an ancient bistable photopigment contained in "intrinsically photosensitive retinal ganglion cells" (RGCs), initiates the signal transduction by which light drives circadian rhythms [112]. Peak activation of intrinsically photosensitive RGCs occurs by light in the range of 460-480 nm, coinciding with the maximal absorption spectrum of melanopsin.…”

Section: In the Beginning There Was Lightmentioning

confidence: 99%

“…RGCs convey light induced signals along the retinohypothalamic tract to a master clock in the suprachiasmatic nuclei (SCN) of the basal hypothalamus for ulterior control of peripheral tissues. The master clock in SCN sensitizes peripheral molecular clocks by neurohumoral means to the light/dark cycle, thereby integrating circadian rhythmicity at the whole-body level [112]. The principal photic resetting cue to the SCN is in the 470 to 480 nm range, the range of wavelengths responsible for maximal RGC activity.…”

Section: In the Beginning There Was Lightmentioning

confidence: 99%

Melatonin Relations with Energy Metabolism as Possibly Involved in Fatal Mountain Road Traffic Accidents

Behn

Gregorio

2020

IJMS

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Previous results evidenced acute exposure to high altitude (HA) weakening the relation between daily melatonin cycle and the respiratory quotient. This review deals with the threat extreme environments pose on body time order, particularly concerning energy metabolism. Working at HA, at poles, or in space challenge our ancestral inborn body timing system. This conflict may also mark many aspects of our current lifestyle, involving shift work, rapid time zone crossing, and even prolonged office work in closed buildings. Misalignments between external and internal rhythms, in the short term, traduce into risk of mental and physical performance shortfalls, mood changes, quarrels, drug and alcohol abuse, failure to accomplish with the mission and, finally, high rates of fatal accidents. Relations of melatonin with energy metabolism being altered under a condition of hypoxia focused our attention on interactions of the indoleamine with redox state, as well as, with autonomic regulations. Individual tolerance/susceptibility to such interactions may hint at adequately dealing with body timing disorders under extreme conditions.

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Multimodal investigation of melanopsin retinal ganglion cells in Alzheimer's disease

Morgia

Mitolo

Romagnoli

et al. 2023

Ann Clin Transl Neurol

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Objective: In Alzheimer's disease (AD), the presence of circadian dysfunction is well-known and may occur early in the disease course. The melanopsin retinal ganglion cell (mRGC) system may play a relevant role in contributing to circadian dysfunction. In this study, we aimed at evaluating, through a multimodal approach, the mRGC system in AD at an early stage of disease. Methods: We included 29 mild-moderate AD (70.9 AE 11 years) and 26 (70.5 AE 8 years) control subjects. We performed an extensive neurophtalmological evaluation including optical coherence tomography with ganglion cell layer segmentation, actigraphic evaluation of the rest-activity rhythm, chromatic pupillometry analyzed with a new data-fitting approach, and brain functional MRI combined with light stimuli assessing the mRGC system. Results: We demonstrated a significant thinning of the infero-temporal sector of the ganglion cell layer in AD compared to controls. Moreover, we documented by actigraphy the presence of a circadian-impaired AD subgroup. Overall, circadian measurements worsened by age. Chromatic pupillometry evaluation highlighted the presence of a pupil-light response reduction in the rod condition pointing to mRGC dendropathy. Finally, brain fMRI showed a reduced occipital cortex activation with blue light particularly for the sustained responses. Interpretation: Overall, the results of this multimodal innovative approach clearly document a dysfunctional mRGC system at early stages of disease as a relevant contributing factor for circadian impairment in AD providing also support to the use of light therapy in AD.

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Melanopsin and the Intrinsically Photosensitive Retinal Ganglion Cells: Biophysics to Behavior

Cited by 184 publications

References 264 publications

Modeling melanopsin‐mediated effects of light on circadian phase, melatonin suppression, and subjective sleepiness

Modeling melanopsin‐mediated effects of light on circadian phase, melatonin suppression, and subjective sleepiness

Melatonin Relations with Energy Metabolism as Possibly Involved in Fatal Mountain Road Traffic Accidents

Multimodal investigation of melanopsin retinal ganglion cells in Alzheimer's disease

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