It is no secret that the eye and the brain work together for both vision and regulating the circadian rhythm. Yet, what is going on at the cellular level and deep within the brain that allows for vision and the sleep/wake cycle to work correctly. Well, as you can guess research is taking place in these two areas, to learn more about how each works and to use this information to develop treatments for diseases and sleep disorders.
Human and Insect Vision Formation
Is it possible that insects and humans share similarities in terms of vision development? Researchers at the University of California Irvine found that they both share similarities and have important differences regarding the production of the critical light-absorbing molecule of the retina, known as 11-cis-retinal.
In this study, researchers used X-ray crystallography to study a protein known as NinaB, which is found in insects and is similar to the RPE65 protein found in humans. The RPE65 protein provides the instructions necessary for making a protein that is crucial for normal vision. NinaB and RPE65 proteins are essential for 11-cis-retinal synthesis and when they aren’t around, the result is severe visual impairment.
While NinaB and RPE65 share a common evolutionary origin and three-dimensional structure, how they produce 11-cis-retinal is very different. The creation of 11-cis-retinal starts with consuming foods that contain beta-caratene, a compound used for vitamin A generation, such as carrots or pumpkins. These nutrients are metabolized by NinaB and RPE65. Humans need both NinaB and RPE65 to make 11-cis-retinal from beta-carotene. Insects, on the other hand, only need NinaB.
Scientists found that they are structurally alike, but where they perform their activities are different. Knowing more about the key features within NinaB led to a greater understanding of the “machinery” needed to support the workings of the retinal visual pigments. Additionally, the study of NinaB provided valuable information about a key part of RPE65 that was not previously known. These findings add more knowledge about how mutations in RPE65 can cause retinal diseases, such as Leber’s congenital amaurosis, a blinding disease that starts in childhood, with the most severe case causing blindness by age one.
How Does the Circadian Rhythm Stay on Track
While rainy days can make a person feel like taking a nap, for the most part, people are awake during daylight hours, regardless of the weather, and they sleep at night. What is going on in our brains that allows that to happen?
Scientists at the Johns Hopkins University School of Medicine and the National Institute of Mental Health, part of the National Institutes of Health identified a protein in the visual system of mice that seems to be key for stabilizing circadian rhythms by buffering the brain’s response to light. The protein that was identified set the groundwork in the brain during neural development to allow for stable responses to the circadian rhythm despite day-to-day changes.
While circadian systems are trained by exposure to light, scientists didn’t know how the brain became “wired” to the mechanisms responsible for the circadian rhythms. So, they searched a database for biological molecules that are present during the development of a mouse’s control center for circadian rhythm, namely the suprachiasmatic nucleus. This is the part of the brain that both mice and humans share. Located within the hypothalamus, the suprachiasmatic nucleus is near the areas that control vision and makes connections with brain cells that lead to the retina.
Researchers eventually found a cell surface protein called teneurin-3, also known as Tenm3. This protein is part of a group of proteins that play an important role in the visual system circuit assembly and in other central nervous system circuits. When they genetically altered mice to prevent Tenm3 production, the mice developed fewer connections between the retina and the suprachiasmatic nucleus compared to mice with Tenm3 that was not altered. However, the mice that didn’t have the Tenm3 did develop more connectivity between cells in the core and shell of the suprachiasmatic nucleus, which is where Tenm3 localizes.
To learn more about Tenm3 and its role relative to circadian rhythms, scientists conducted a set of experiments. First, they trained mice both lacking and with the Tenm3 on a 12-hour light/dark cycle, then they shifted the dark period ahead by six hours. Mice with the Tenm3 needed four days to adjust to their circadian rhythm to the shift. Mice without the Tenm3 adjusted in two days. This suggests that Tenm3 helps to wire the brain the keep stable circadian rhythms even when light exposure is variable. Further study of Tenm3’s role may lead to treatments for jet lag and sleep disorders.
Research once again shows there is more to the inner workings of vision and the circadian rhythm than meets the eye. Proteins involved in the vision of humans and insects share a common origin, but how they do their work is very different. Circadian rhythms are regulated not just by light, but by a specific protein. While there is more to learn about vision formation and circadian rhythms, the insights gained from these research projects will both increase our knowledge about them and possibly lead to treatments for diseases like, Leber’s congenital amaurosis, and sleep disorders.
https://medlineplus.gov/genetics/gene/rpe65
https://eyewiki.aao.org/Leber_Congenital_Amaurosis