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Melanopsin: how your eyes tell your body what time it is

What melanopsin is, how a small set of light-sensing cells in your eye set your body clock, why they respond most to blue-cyan light, and what melanopic lux means.

Melanopsin is a light-sensitive protein in a small group of cells at the back of your eye. These cells do little for normal vision. They mostly measure how much light is around you and send that to the part of your brain that runs your body clock.

How melanopsin was discovered

For most of the 20th century, scientists assumed the eye had two kinds of light sensors, rods for dim light and cones for color and detail. Then in the 1990s, researchers found that mice whose rods and cones had died from a genetic disease still shifted their body clocks in response to light, so some other cell in the eye had to be detecting it.

In 1998 Ignacio Provencio and colleagues found a new light-sensitive protein in the skin of frogs, in pigment cells called melanophores, and named it melanopsin 1. Two years later they found it in the human retina, in a layer of nerve cells in front of the rods and cones 2.

In 2002, two papers in the same issue of Science showed what it was doing. David Berson's lab found that the nerve cells connecting the rat eye to the brain's master clock respond to light on their own, even when signals from the rods and cones are blocked with drugs 3. Samer Hattar and colleagues showed these were the cells that contain melanopsin, and traced their wiring to the master clock 4. They are now called intrinsically photosensitive retinal ganglion cells, or ipRGCs.

What melanopsin cells do in the eye and brain

They make up only a small share of the nerve cells leaving the eye, and they report the overall light level to the brain. The main target is the suprachiasmatic nucleus, a cluster of cells above where the optic nerves cross, which keeps the body clock on time. They also feed the areas that control how wide your pupils open, how alert you feel, and the release of melatonin at night.

Some of the clearest evidence comes from blind people. In a 1995 study, bright light lowered melatonin in some blind patients who couldn't consciously see any light at all, and the effect disappeared when their eyes were covered 5. In 2007, researchers tested two people with a genetic condition that had destroyed their rods and cones. In the man, blue light lowered melatonin, shifted his body clock and made him more alert, more than yellow-green light did. The woman's pupils narrowed most to light around 480 nm, and she could tell when a faint light of that color was on, though not other colors 6. This only happens in some blind people. When the eyes themselves are lost or the optic nerve is damaged, the body clock usually can't get any light signal.

Why melanopsin responds most to blue light

Melanopsin is most sensitive to light around 480 nm, a slightly greenish blue 67. The cones you see brightness with are most sensitive around 555 nm, in the yellow-green. So how bright a light looks to you isn't a reliable guide to how much it affects your clock.

Relative sensitivity400450500550600650700750Wavelength of light (nm)Melanopsin, peak 480 nmBrightness we see, peak 555 nmMelanopsin barelyresponds to red

Daylight has plenty of blue, so it's a strong signal. For the same reason, a cool white LED or a bright screen at night reads to these cells as daytime, while warm, dim light has far less effect. Are LED lights bad for sleep covers which bulbs to buy. Melanopsin responds very little to red light. The guide to light colors at night goes through what that means for bulbs, screens and blue-blocking glasses.

Rods and cones also send signals into the ipRGCs, so melanopsin isn't the only input to the clock. Early in a light exposure, and in dim light, cones do more of the work. Over longer exposures, melanopsin does more 8.

Why longer light exposure has more effect

Rods and cones respond within a fraction of a second and adapt quickly, which is what lets you see well in both a dark room and full sun. These cells are slow. They take seconds to respond and keep firing for as long as the light stays on 3.

So these cells respond much more to an hour of light than to a quick flash. In one study, green light was nearly as strong as blue at lowering melatonin at the start of a six-and-a-half-hour exposure, but its effect faded over the hours while blue held steady 8. The morning sunlight guide has more on how long to spend outdoors, and the guide to daytime light and sleep explains how indoor days change your response to light at night.

Why light at night affects your body clock more

Your body clock is most sensitive to light during your biological night, roughly from a couple of hours before your usual bedtime until around the time you wake. In the middle of the day, the same light shifts the clock very little 9. Melatonin is made only at night, so night is also the only time light can lower it. Light in the evening moves the clock later, and light around and after your usual wake time moves it earlier.

What melanopic lux means

Ordinary lux measures light by how bright it looks to the human eye, so it's weighted toward the yellow-green that cones see best. It tells you little about how much a light affects your clock.

In 2018 the International Commission on Illumination published a standard way to measure light by its effect on melanopsin instead 10. The main unit is melanopic EDI (equivalent daylight illuminance), also called melanopic lux. It's the number of lux of daylight that would stimulate melanopsin as much as the light you're measuring. For daylight, the two numbers are about the same. For warm white bulbs the melanopic number is a good deal lower than the lux reading, and for cool white bulbs it's closer to it.

In 2022 a group of researchers used this unit to recommend light levels for healthy adults, measured at eye level facing forward 11:

  • During the day, at least 250 melanopic lux. Outdoor daylight is far above this, even on a cloudy day, but many offices and homes are below it.
  • In the evening, starting at least three hours before bed, no more than 10 melanopic lux.
  • During sleep, as dark as possible, and no more than 1 melanopic lux.

These are targets for the average person. Sensitivity to evening light varies a lot from one person to the next 12, and the evening light guide has more on that.

When to see a doctor

If you have trouble sleeping most nights or feel very sleepy in the day, talk to a doctor.

Turn this into a plan for your day.

Answer a few questions about your schedule and light access, and Calibrate builds a daily light-timing plan around the day you actually live.

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References

  1. Provencio I, Jiang G, De Grip WJ, Hayes WP, Rollag MD (1998). Melanopsin: an opsin in melanophores, brain, and eye. PNAS 95(1):340-345. doi.org/10.1073/pnas.95.1.340
  2. Provencio I, Rodriguez IR, Jiang G, et al. (2000). A novel human opsin in the inner retina. J Neurosci 20(2):600-605. doi.org/10.1523/JNEUROSCI.20-02-00600.2000
  3. Berson DM, Dunn FA, Takao M (2002). Phototransduction by retinal ganglion cells that set the circadian clock. Science 295(5557):1070-1073. doi.org/10.1126/science.1067262
  4. Hattar S, Liao HW, Takao M, Berson DM, Yau KW (2002). Melanopsin-containing retinal ganglion cells: architecture, projections, and intrinsic photosensitivity. Science 295(5557):1065-1070. doi.org/10.1126/science.1069609
  5. Czeisler CA, Shanahan TL, Klerman EB, et al. (1995). Suppression of melatonin secretion in some blind patients by exposure to bright light. N Engl J Med 332(1):6-11. doi.org/10.1056/NEJM199501053320102
  6. Zaidi FH, Hull JT, Peirson SN, et al. (2007). Short-wavelength light sensitivity of circadian, pupillary, and visual awareness in humans lacking an outer retina. Curr Biol 17(24):2122-2128. doi.org/10.1016/j.cub.2007.11.034
  7. St Hilaire MA, Ámundadóttir ML, Rahman SA, et al. (2022). The spectral sensitivity of human circadian phase resetting and melatonin suppression to light changes dynamically with light duration. PNAS 119(51):e2205301119. doi.org/10.1073/pnas.2205301119
  8. Gooley JJ, Rajaratnam SMW, Brainard GC, et al. (2010). Spectral responses of the human circadian system depend on the irradiance and duration of exposure to light. Sci Transl Med 2(31):31ra33. doi.org/10.1126/scitranslmed.3000741
  9. Khalsa SBS, Jewett ME, Cajochen C, Czeisler CA (2003). A phase response curve to single bright light pulses in human subjects. J Physiol 549(3):945-952. doi.org/10.1113/jphysiol.2003.040477
  10. Commission Internationale de l'Eclairage (2018). CIE S 026/E:2018. CIE system for metrology of optical radiation for ipRGC-influenced responses to light. Vienna: CIE. doi.org/10.25039/S026.2018
  11. Brown TM, Brainard GC, Cajochen C, et al. (2022). Recommendations for daytime, evening, and nighttime indoor light exposure to best support physiology, sleep, and wakefulness in healthy adults. PLoS Biol 20(3):e3001571. doi.org/10.1371/journal.pbio.3001571
  12. Phillips AJK, Vidafar P, Burns AC, et al. (2019). High sensitivity and interindividual variability in the response of the human circadian system to evening light. PNAS 116(24):12019-12024. doi.org/10.1073/pnas.1901824116
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