Retina has its own circadian rhythm

VENTURIST/CC-BY-2.0 The circadian rhythm, which regulates sleep cycles, is more complicated than was thought.

VENTURIST/CC-BY-2.0
The circadian rhythm, which regulates sleep cycles, is more complicated than was thought.

By JOAN YEA
Senior Staff Writer

The suprachiasmatic nucleus (SCN), a wing-shaped structure in the hypothalamus, operates as the body’s internal clock, synchronizing circadian rhythms of separate tissues to generate an approximately 24-hour circadian cycle for the entire body.

Numbering in several thousands of neurons on either wing, the SCN depends on signals from light-sensitive pigments in the retina for the photoentrainment process. Light cycles sensed by these photosensitive proteins in the retina enable the SCN to reset the body’s clock in accordance with the external environment.

Researchers, however, have recently discovered that not all of the photosensitive proteins in the retina are geared toward resetting the SCN. As described in an article published online on Sept. 21 in the journal Proceedings of the National Academy of Sciences, one specific photopigment allows the retina to set its own circadian rhythm independently of the tempo determined by the body’s master clock. Researchers from the Johns Hopkins School of Medicine and the University of Washington Medical School used genetically-engineered mice in their investigation of the function of certain photopigments in the retina.

Of the seven opsin proteins, photopigments, which are present in the mammalian retina, were of primary interest, along with the proteins OPN3 (encephalopsin) and OPN5 (neuropsin). Opsin proteins are light-sensitive proteins found in the retina.

Though commonly found in neural mammalian tissue, the function of OPN3 has not been determined. The researchers of this study devised an approach to see whether the mice lacking the OPN3 gene still displayed signs of retinal photoentrainment, which means whether the retina could train itself to follow the patterns of light and darkness in the environment.

The investigators discerned less robust activity patterns in the eye without OPN3, but otherwise the retina displayed continued light sensitivity. However, the lack of OPN5 led to an impaired retinal ability to adapt to cycles of light and darkness.

To ensure that the absence of OPN5 and not overall retinal dysfunction caused the disruption of the retinal photoentrainment process, the researchers conducted various tests. The results yielded a surprising implication — local photoentrainment of the retina does not depend on the photopigments utilized for the entrainment of the SCN. In other words, the genetically engineered mice lacked OPN5 but possessed intact and functioning photosensitive cells such as rods, cones and OPN4 (melanopsin) which are necessary for the resetting of the SCN.

In addition to investigating the absence of OPN5 on local retinal photoentrainment, the investigators conducted experiments with different wavelengths of light to determine whether OPN5 would be more sensitive to different wavelengths than other opsin proteins. In contrast with other photoreceptor cells, OPN5 was identified to be most responsive to Ultraviolet (UVA) and violet light which bolstered the research team’s finding that some separate light signals control the retina’s molecular clock while others set the body’s master clock.

Although the investigators have neither determined the type of cell that expresses OPN5 nor the nature of the signaling mechanism by which OPN5 controls local photoentrainment within the scope of this study, the research team posits that the OPN5 signaling pathway is a functionally unique circuitry.

It is possible that signals originating from OPN5 may depend on coded electrical or chemical signals different from the action potential electrical signals utilized by the pathway from rods, cones and OPN4 to the SCN.

Possible reasons for this differentiation between light signaling pathways present an area for further study. According to the research team, the division of labor among retinal pigments may suggest a selective advantage in separate photoentrainment processes. While OPN5 is not required for SCN photoentrainment, it is necessary for the local photoentrainment of the retina and the cornea.

The investigators also recognized in their efforts to identify the function of OPN5 that the cornea of the eye showed signs of local photoentrainment separate from the entrainment of the SCN.

Corneal local photoentrainment processes, as in the case with retinal photoentrainment, continued in the genetically engineered mice lacking OPN3 and malfunctioned in the rodents without OPN5. To the researchers’ knowledge these findings are the first to establish evidence for photosensitive elements in the mammalian cornea which was previously thought to be incapable of photoreception.

Though the investigators are perplexed as to the exact nature of OPN5 signaling in the cornea, they have adduced compelling evidence for the function of the formerly unknown function of OPN5 and intend to further inquire about the nature of this local photoentrainment process in the retina and cornea.

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