Melanopsin

There are various environmental temporal cues that can be used as synchronizing agents for the circadian expression of living beings, including social interaction, physical activity and feeding. However, there is a consensus that the main synchronizing agent of circadian rhythmicity is the light/dark cycle. Find out more in the article by Circadian rhythm.

In humans, as in all mammals, the only photoreceptor organ is the retina, a structure present in the eyes whose purpose is to process light information, thus making vision possible. It is therefore plausible to imagine that it is through vision that we perceive changes in light/dark. However, things are not as simple as they seem.

In experimental work with mice, it has been observed that in individuals who are congenitally blind (through genetic manipulation), it is still possible to observe circadian responses to light, thus suggesting that the information regulating the endogenous circadian timing system is independent of the perception of visual processes in the retina (Foster, 1993). Additionally, in mice that lack cones and rods (congenital, through genetic manipulation), it is possible to observe that circadian expression through light/dark is not significantly affected (Yoshimura and Ebihara, 1996, 1998).

From these facts, it can be assumed that circadian synchronization does not depend on the visual perception of light. In the early 2000s, the existence of photoreceptor ganglion cells in the retina (ipRGCs) was discovered, with the presence of melanopsin. These photoreceptors have direct communication with the suprachiasmatic nuclei, which play an essential role in the circadian timing system (Beerson et al 2002).

As in rodents, circadian system responses to light stimuli do not depend on the presence of retinal cones and rods. This role can only be played by ipRGCs, although they communicate indirectly with cones and rods, receiving information that is also used for circadian timing adjustments.

In recent studies, the authors describe how the information processed by cones and ipRGCs plays different roles in the circadian timing system. Gooley et al. (2010) carried out a study with humans using light exposure therapy in order to identify changes in melatonin secretion and changes in circadian expression. However, as well as using a blue spectrum light (460nm), which is the most sensitive wave frequency for ipRGCs, they also used a green spectrum light (555nm), which is more sensitive to the retinal photoreceptor cell system, the cones.

As a result, the authors observed that blue spectrum light plays a role in Omelatonin suppression when compared to green spectrum light, in which only an initial decrease in melatonin secretion is observed. However, the phase shifts observed in the expression of the circadian rhythm of melatonin are very similar, with green light therapy resulting in greater phase shifts than blue light therapy.

Based on this data, there is a concern to prevent not only the emission of predominantly blue-spectrum light by electronic devices in the home. Green-spectrum light can also generate phase delays in circadian rhythmicity, which can lead to delays in going to sleep and waking up.

These results are extremely important when it comes to strategies for developing and optimizing light therapies in the treatment of sleep disorders and circadian rhythmicity. In addition to the timing of light therapy, it is also necessary to manipulate the spectrum, duration and patterns of light in order to stimulate both the melanopsin and cone receptor systems. Or even to be able to choose the best type of intervention, whether or not melatonin suppression is necessary during treatment. The authors also describe that the joint activation of melanopsins and cones in different light spectra can be effective in maintaining circadian expression in confined environments, such as space expeditions, submarines, among others. And we can also extrapolate the implementation of related therapies in situations where people are not routinely exposed to light, such as in long-stay institutions (nursing homes), hospitals (ICUs, for example) and even in strategies on long transcontinental flights, where the change of time zone generates rhythm disturbances caused by social jetlag.