A remarkable study from researchers at the Salk Institute has uncovered a profound new insight into how our circadian rhythms are regulated through light-sensing mechanisms within our eyes. The research could lead to new ways to combat insomnia and help reset the internal clocks of people with disrupted circadian rhythms.

We know that our circadian rhythms are fundamentally driven by exposure to light, and we also know that artificial blue light can disrupt those natural 24-hour rhythms. But how do our bodies actively sense light and adapt their circadian rhythm accordingly? Well, it comes down to a small volume of retinal cells in the back of our eyes and a recently discovered light-sensitive retinal protein called melanopsin.

Melanopsin was only identified less than two decades ago and its discovery helped define a new class of retinal cells. Alongside the rods and cones in our eyes we have a small amount of innately photosensitive cells. These cells are designed to not help us see, but rather sense light as part of our circadian management system.

When these specific retinal cells sense light, they produce melanopsin, which directly tells certain parts of our brain to stay awake and alert. As well as suppressing melatonin, melanopsin has been found to help regulate and set our body's circadian rhythm.

"Compared to other light-sensing cells in the eye, melanopsin cells respond as long as the light lasts, or even a few seconds longer," says Ludovic Mure, first author of the paper. "That's critical, because our circadian clocks are designed to respond only to prolonged illumination."

The new study set out to uncover exactly what molecular mechanism occurs when melanopsin cells are triggered by light. Generally, proteins called arrestins act to block the activity of certain receptors, however, this research unexpectedly revealed that the continual melanopsin activity in the eye was actually maintained by the interaction between two particular arrestins.

Animal studies revealed that two arrestins (beta arrestin 1 and beta arrestin 2) worked together to maintain continued melanopsin activity in the presence of light stimulation. When one of those arrestins was blocked, melanopsin regeneration was disrupted suggesting this mechanism helps manage the continual signal to the brain that there is light and we should stay alert.

"Our study suggests the two arrestins accomplish regeneration of melanopsin in a peculiar way," says Satchidananda Panda, senior author on the study. "One arrestin does its conventional job of arresting the response, and the other helps the melanopsin protein reload its retinal light-sensing co-factor. When these two steps are done in quick succession, the cell appears to respond continuously to light."

The hypothesis following on from this research is that by understanding how light sensed by the eye can help set our circadian rhythm, we can hopefully produce treatments for a huge variety of disorders. If light from our digital screens is artificially overstimulating melanopsin and disrupting our circadian rhythm, maybe this mechanism can be interrupted using drugs. Or maybe some people suffering from insomnia could have their circadian clocks chemically reset by triggering this mechanism. Panda and the research team at Salk will be turning their focus towards these questions for the next stages of their work.

The new study was published in the journal Cell Reports.