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Circadian Lighting Personal

inTRO to ipRGCs

Rods, cones, and…ipRGCs?

For almost a century and a half, it was thought that the mammalian retina had just two types of photoreceptors: rods and cones. That assumption was not proven to be false until studies in the late 1990s proved the existence of a third kind of mammalian photoreceptor that differed greatly from rods and cones. These new types of photoreceptors were retinal ganglion cells (RGCs) that were intrinsically photosensitive (ipRGCs)— or in other words, naturally sensitive to light.

Though the official evidence to determine that ipRGCs actually existed did not come until much later, this third class of photoreceptor had already been hypothesized in 1927, nearly seven decades earlier, by a graduate student named Clyde Keeler. During one of his studies, he examined the behavior of mice that lacked nearly all rod and cone function as a result of severe retinal degradation, which left them functionally blind. Keeler noticed that despite the lack of rods and cones, the mice still had a very strong and significant pupillary constriction in response to light, and he determined that this response must have been the result of some third photoreceptor in the retina. The lack of concrete evidence for a whole new photoreceptor at the time resulted in this pupillary response being explained away by other scientists. However, in 1999, Russell Foster and his team would revisit Keeler’s work armed with a new host of tools.

Foster et al. worked with mice, much like Keeler did, but in their case, the mice being observed were genetically engineered to not have any rods or cones. Yet regardless of their missing rods and cones, the rats still displayed strong pupillary light reflexes and were even able to shift their circadian rhythms with shifting light exposure schedules. With these studies complete, the presence of a third photoreceptor was almost confirmed, but some still weren’t convinced because nobody had found another light-sensitive molecule (opsin) in the mammalian retina yet.  

The discovery of melanopsin in the photosensitive skin cells of frogs occurred in 1998, and in the following four years studies determined that the very same opsin was being expressed in a small percent of RGCs in both mouse and human retinas. This discovery allowed scientists to easily mark ipRGCs and confirm their existence, which finally put to rest the debate of whether or not there was a third class of photoreceptor.

So they exist, but what do they do?

IpRGCs differ greatly from rods and cones when it comes to how they work. Their main function in the body is to signal the intensity of ambient light levels (irradiance) to the brain. These signals are largely used for non-image-forming visual reflexes that are subconscious, such as pupillary constriction, neuroendocrine regulation, and synchronizing daily circadian physiological rhythms to environmental light. This means that the way ipRGCs respond to light by themselves is also quite different from rods and cones.

As mentioned before, these photoreceptors use melanopsin as their photopigment. and that makes them more responsive to light at around 480nm (blue light). In the graph below, you can see that this wavelength is significantly different from the best wavelengths for stimulating rods and cones (panel b).

From: https://webvision.med.utah.edu/book/part-ii-anatomy-and-physiology-of-the-retina/melanopsin-expressing-intrinsically-photosensitive-retinal-ganglion-cells/

Although ipRGCs function as photoreceptors themselves, it was found that they additionally receive synaptic input from the circuits of rods and cones. This means that ipRGCs have both an intrinsic light response coming from melanopsin and an extrinsic one that is mediated by synaptic input from rods and cones. The light response caused by melanopsin is markedly different from that of rods and cones: ipRGCs have both an intrinsic and sluggish light response as well as an extrinsic, rod/cone driven, rapid photoresponse. There is an ongoing debate about the relative significance of this extrinsic synaptic input and the role rods and cones play in determining our circadian rhythms.

A recent case study:

In a recent research article by Mouland et al., their team assessed whether the effective light intensity registered by melanopsin (blue light ~480nm) was a more important determinant of circadian impacts than that of cones under realistic contrast scenarios. The ability to determine melanopsin’s contribution to circadian light responses comes from the evolution of a color science technique which is referred to with multiple names, such as receptor silent substitution or metamerism in colorimetry. Metamerism occurs when two colors appear to match under a specific lighting condition but have different underlying spectra. 

From: https://en.wikipedia.org/wiki/Metamerism_(color)

This technique allows for the stimulation of specific photoreceptor classes, like ipRGCs. Mouland and colleagues quantified the circadian impacts of different photoreceptors by recording electrophysiological activity from the suprachiasmatic nucleus (SCN) of anaesthetised mice while they were presented with movies. The movies were either high or low contrast and had varying irradiances specialized for the distinct photoreceptor classes. 

During the experiment, the energy response recorded from the SCN closely tracked with melanopsin-driven signaling across all conditions. In general, steps in melanopic irradiance were determined to be the most significant factor accounting for light-induced changes in SCN activity. The only cone-directed lighting patterns with significant impacts on SCN activity were low contrast movie conditions. Basically, this study suggests that cones do have an impact on the circadian signal going to the SCN in some conditions, but the influence of melanopsin on the circadian signal is far more consistent.

This blog post was written by Arcascope’s intern, Ali Abdalla. Thanks, Ali!

This post used Webvision as a major resource. Thanks to Dustin Graham and Kwoon Wong for the excellent review.

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Circadian Personal Sleeping Troubles

Measuring Sleep Regularity

What is sleep regularity and why is it important?

Sleep regularity is a gauge of how consistent a person’s sleep patterns are, based on the day-to-day variability in their sleep–wake times. In general, having poorer sleep regularity, or irregular sleep patterns, has been shown to lead to many adverse outcomes in metabolism, mental health, and cognitive performance. Low sleep regularity has even been linked to increased inflammation. In order to avoid these and other complications, you want to increase your sleep regularity by aiming to get into bed at the same time every night.

How can we score sleep regularity?

There are at least five different metrics that can be used to quantify sleep regularity, each capturing different aspects of it and useful in its own way. The five measures of sleep regularity that we’ll look at in this blog post are listed below:

Traditional/Overall Metrics:

  • Individual Standard Deviation (StDev)
  • Interdaily Stability (IS)
  • Social Jet Lag (SJL)

Newer Metrics:

  • Composite Phase Deviation (CPD)
  • Sleep Regularity Index (SRI)

Traditionally, the most common overall metrics that have been used to assess sleep regularity are quantified by measuring sleep deviations in sleep patterns from an individual’s average. Examples of overall metrics are StDev and IS, both of which compare sleep from each day to an average sleep–wake pattern, and SJL, a metric that compares two average sleep patterns (workdays and free days).

StDev: lower is more regular / StDev⬇ = Sleep regularity⬆

This score is just the standard deviation of your sleep metric of choice, like sleep onset, sleep offset, or sleep midpoint. The standard deviation captures the variation of a quantity from its mean. 

IS: higher is more regular / IS⬆ = Sleep regularity⬆

This metric uses sleep-wake data (can also use rest-activity data) over a period of days to measure the stability of a person’s sleep-wake rhythms. It does this by comparing the pattern of daily sleep activity to the average pattern across many days. 

SJL: lower is more regular / SJL⬇ = Sleep regularity⬆

Social jet lag is a metric that quantifies the mismatch in the average mid-sleep timing between workdays and free days. Negative SJL values represent earlier mid-sleep timing on weekends than weekdays while positive values indicate the opposite.

Two newer measures of sleep regularity are CPD and SRI. These two fall under the category of consecutive metrics, which means they measure variability in sleep–wake patterns between consecutive days. The circadian system makes adjustments daily, and consecutive metrics were developed in order to utilize day-to-day information and more accurately predict circadian disruptions associated with poor sleep regularity.

CPD: Lower is more regular /  CPD⬇ = Sleep regularity⬆

Composite phase deviation is a metric that was created with shift workers in mind. CPD quantifies circadian disruption where sleep is both irregular (rotating shifts) and mistimed (sleeping in daytime). This metric uses an individual’s chronotype to determine optimal timing of sleep. The chronotype then helps to quantify how “mistimed” they are. The regularity aspect is calculated using the difference between mid-sleep timing from one day to that of the prior day. In order for CPD to be derived it requires data that has one main sleep session per day or some other daily sleep variable, like sleep duration.

SRI: higher is more regular /  SRI⬆ = Sleep regularity⬆

The sleep regularity index is a measure based on binary sleep-wake time series. It measures the similarity of a person’s sleep-wake pattern from one day to the next. The scale for this metric ranges from 0 (random) – 100 (perfectly regular) and it represents the percentage probability that an individual will be in the same sleep/wake state at any two time points. It’s important to note that this metric does not account for total sleep time so a person that (hypothetically) sleeps 0% of the time will still be able to get an SRI value of 100.

So I’m regular, that means I’m healthy right?

Well, not quite. Depending on the kind of variability you have in your sleep patterns and the method used to record your sleep, different metrics may tell you very different stories regarding your sleep regularity. Context is very important when making a decision about which sleep regularity metric to use. 

Just think about what would happen if you increased the variability in your work week sleep timing, but maintained a consistent average. Your SJL score would stay the same, while your other metrics would likely shift to indicate greater variability. The ordering of days also matters. In Fischer et al. they shuffle days around to show how consecutive metrics can give you different stories on regularity than overall metrics do.  

In order to properly assess sleep regularity for yourself or your patients, it is necessary to understand the little things that go into calculating each of these sleep metrics. A variety of unknowns, such as the type of data being gathered or the length of the data set, can cause these metrics to disagree with each other. The good news is that you’ve got lots of options to choose from. 

This blog post is heavily based on “Measuring sleep regularity: Theoretical properties and practical usage of existing metrics” by Fischer et al. The authors didn’t have anything to do with the making of this post, but we want to thank them for writing an inspiring paper. 

This post was written by Arcascope’s intern, Ali Abdalla. Thanks, Ali!

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Circadian Personal Sleeping Troubles

What School Never Taught You

I woke up feeling groggy and lazy almost every day in the past school semester leading up to this summer. I was already doing research on sleep at that point, and I had a general idea about what I was doing wrong, but when I tried to dive deeper into the hundreds of articles on sleep science, I just found myself getting tired and confused. The last few months working as an intern at Arcascope have taught me how to get in sync with my circadian rhythms and taught me of the many subtleties that are involved with supporting your circadian system.

When I started learning about sleep, I found myself asking friends about their habits and experiences with sleep out of curiosity. I quickly realized that almost everyone I talked to had experienced frustrating sleep problems at some point during their lives and had no idea how to deal with them because they were just never taught enough about sleep. I decided that I wanted to give them some of the knowledge that they will need to improve their sleep quality by reflecting on certain essential components of sleep that I have learned about throughout this past summer.

I want to begin this informational recap by stating what I think is the most important factor involved in getting good sleep: Get enough light and get it only when you are supposed to. Getting light, especially bright light, at the wrong times causes an advance or delay to your circadian clock which essentially means that you’re giving yourself jet lag without ever having to leave your room. Light is the strongest signal to the human circadian system and it can do some amazing things when used correctly. Bright light has the ability to affect the amplitude of your circadian clock, and if you time it right, can allow you to cross time zones faster than you otherwise would. However, this kind of entrainment schedule can be especially hard to follow given the pervasiveness of screen use at night. The presence of almost any light, particularly above 50 lux, has been shown to have a melatonin suppressing effect that can make the process of falling or staying asleep difficult.

Using light as effectively as possible is not just about timing and brightness but also about daily regularity. Previous light history has been shown to affect your circadian clocks current sensitivity to light, which makes paying attention to your light exposure important to maintain your healthy sleep habits. Poor sleep regularity has been linked to many health complications ranging from subdued cognitive performance all the way to inflammation. Recently, some new metrics have been created to quantify sleep regularity which may give clinicians the chance to make more well-informed decisions regarding recommendations for their patients’ sleep health.

The timing and brightness of light, as well as the regularity of your sleep schedule, are three components that have an immense influence on overall sleep health. My personal experience in school so far has left me lacking this key knowledge on how to promote my sleep efficiency. Learning about what to be cognizant of in regards to my sleep habits has greatly increased my alertness in the early morning, and I still have lots of room to improve upon my habits. The crux of my argument here is that just being aware of the things that can mess with your sleep will inherently allow you to avoid bad situations and improve the quality of your sleep.

This post was written by Arcascope’s intern, Ali Abdalla. Thanks Ali!

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Shift Work Sleeping Troubles

Shift Work Disorder

What Exactly is Shift Work Disorder?

Shift work disorder, or SWD, is a type of circadian rhythm sleep disorder which is caused by working shifts that do not fall within the conventional working hours of around 9 am – 5 pm. These shifts overlap with periods of significant light sensitivity which can cause shift workers to be particularly vulnerable to having dysfunctional circadian rhythms.