Scientists discover how certain cells of the retina respond to artificial lighting – (Reporting)


For most, the time spent looking at screens – on computers, phones, iPads – is many hours and can often disrupt sleep. Now researchers at the Salk Institute have identified how certain cells in the eye process ambient light and redefine our internal clocks, the daily cycles of physiological processes known as the circadian rhythm. When these cells are exposed to artificial light late into the night, our internal clocks can become confused resulting in a number of health problems.

The results, published on November 27, 2018, in Cell Reports, can help lead to new treatments for migraines, insomnia, jet lag and circadian rhythm disorders, which have been linked to cognitive dysfunction, cancer, obesity, insulin resistance, metabolic syndrome and more.

"We are continuously exposed to artificial light, either from screen time, spending the day indoors or staying up late into the night," says Professor Salk Satchin Panda, senior author of the study. "This lifestyle causes ruptures in our circadian rhythms and has deleterious consequences on health."

The back of our eyes contains a sensitive membrane called the retina, the innermost layer of which contains a small subpopulation of light-sensitive cells that operate like pixels in a digital camera. When these cells are exposed to continuous light, a protein called melanopsin continuously regenerates within them, signaling ambient light levels directly to the brain to regulate consciousness, sleep, and alertness. Melanopsin plays a crucial role in the synchronization of the internal clock after 10 minutes of illumination and, under strong light, suppresses the hormone melatonin, responsible for regulating sleep.

"Compared to other light-sensitive cells in the eye, melanopsin cells respond as the light lasts, or even a few seconds longer," says Ludovic Mure, a team scientist and first author of the article. "This is critical because our circadian clocks are designed to respond only to prolonged lighting."

In the new paper, Salk researchers used molecular tools to activate melanopsin production in retinal cells in mice. They found that some of these cells have the ability to sustain light responses when exposed to repeated long pulses of light, while others become desensitized.

Conventional wisdom has held that proteins called arrestins, which disrupt the activity of certain receptors, should disrupt the photosensitive response of the cells seconds after the lights come on. The researchers were surprised to find that the arrestinas are indeed necessary for the melanopsin to continue responding to prolonged lighting.

In mice without any of the versions of the arrestin protein (beta-arrestin 1 and beta-arrestin 2), retinal melanopsin-producing cells failed to maintain their sensitivity to light under prolonged lighting. The reason is that arrestin helps to regenerate melanopsin in the cells of the retina.

"Our study suggests that the two prisons perform the regeneration of melanopsin in a peculiar way," says Panda. "One arrestin does its conventional job of stopping the response, and the other helps the melanopsin protein recharge its light-detecting cofactor on the retina. When these two steps are done in rapid succession, the cell appears to respond continuously to light.

By better understanding the interactions of melanopsin in the body and how the eyes react to light, Panda expects to find new targets to combat distorted circadian rhythms due, for example, to artificial lighting. Previously, Panda research team found that chemicals called opsinamides could block the activity of melanopsin in mice without affecting their vision, offering a potential therapeutic pathway to address the hypersensitivity to light experienced by people suffering from migraine. Researchers then want to find ways to influence melanopsin to redefine internal clocks and help with insomnia.

This work was supported by Leona M. and Harry B. Helmsley Charitable Trust, the National Institutes of Health and the Glenn Foundation.


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