The eye is like a security camera that captures images that are both at rest and in motion. From our eyes, images travel through the retina and go to the brain. This information allows us to perform a myriad of tasks from reading, creating a meal to navigating from Point A to Point B. In addition, the light that comes into our eyes helps to regulate our circadian rhythm. How is medical research adding to our understanding of how our eyes evolved so that they do what they do. Projects at the University of California Berkeley (UC Berkeley) and Johns Hopkins University, show the origins of retinal cells and how the visual system regulates the circadian rhythm.
Evolution of the Retina
How does one find out about the evolution of the retina of vertebrate species? A group of scientists from UC Berkeley collected cow and pig eyes from butchers and what they found from these and eyes from other species helped to increase understanding about the how vertebrate retina evolved.
Researchers in the lab of Karthik Shekhar, assistant professor of chemical and biomolecular engineering in the College of Chemistry, did a comparative analysis of the cell types in the retina and they learned that most cell types have an ancient evolutionary history. These cell types are characterized by their differences at the molecular level, giving clues to their function.
Shekhar’s team discovered that the “midget” retinal ganglion cell, which is responsible for the ability to see fine details, is found in mammals other than primates. Previously, it was thought that this kind of cell was unique to primates. Through the analysis of large-scale gene expression data by way of statistical inference approaches, researchers found evolutionary counterparts of the “midget” retinal ganglion cells in other mammals, though they occurred in smaller proportions. “The early vertebrate retina was probably extremely sophisticated,” said Shekhar. “But the parts list has been used, expanded, repurposed or refurbished in all the species that have descended since then.”
One theory of vision that came about via this research is that as the primate brain became more complex, it relied less on signal processing in the eye, which is key to actions such as reacting to a predator and relied more on analysis within the visual cortex. As a result, there are fewer of these cell types in the human eye. In other words, one species needs to react quickly and another species needs to think before reacting.
The information found in this research could help with research on human eye diseases, like glaucoma. While mice are used extensively in the study of glaucoma only 2 to 4 percent of retinal ganglion cells in mice are midget cells. In contrast, 90 percent of the retinal ganglion cells in humans are midget cells. Knowing about the midget cell counterparts in mice will help to better design and interpret the glaucoma mouse model.
Visual System’s Role in Circadian Rhythms
Circadian rhythms are the changes an organism experiences in a 24-hour period. It influences sleep patterns, hormone release, appetite and digestion and body temperature. In humans it is regulated by the amount of light the eye receives. Yet, what happens there is a rapid change in the amount of light that comes into the eye, such as during a rainy day? While a person might feel a little sad during a damp and overcast day, with the exception of those who have season affective disorder, he or she is able to function and do what needs to be done, as if it were a bright and sunny day. Scientists at Johns Hopkins University identified a protein in the visual system of mice that seems to be significant for stabilizing the body’s circadian rhythms by buffering the brain’s response to light.
The circadian rhythm is trained by exposure to light. At its simplest, the less light that enters the eye, the more of the hormone melatonin the brain makes, which makes a person sleepy. While researchers have learned a lot about the mechanisms responsible for the circadian rhythm, no one knew how the brain becomes wired for them.
Enter scientists in the lab of Alex Kolodkin, Ph.D., professor in the Johns Hopkins Department of Neuroscience and deputy director for the Institute for Basic Biomedical Sciences. They searched a database for molecules present during the development in a mouse’s control center for the circadian rhythms, known as the suprachiasmatic nucleus (SCN). The SCN is located within the hypothalamus, and it is also near the part of the brain that controls vision and makes connections with cells that lead to the retina.
They found a cell surface protein known as teneurin-3 (Tenm3). This protein is part of a group of proteins that play a role in the visual system circuit assembly. When researchers genetically altered mice to prevent the production of Tenm3, the mice developed fewer connections between the retina and the SCN, compared with mice didn’t have their Tenm3 altered. Yet, the mice that didn’t have Tenm3 had developed more connectivity between cells in the core and shell of SCN, where the Tenm3 gathers.
To learn more about how Tenm3 stabilizes circadian rhythms, researchers did a series of experiments. First, they trained the mice that didn’t have Tenm3 on a 12-hour light/dark cycle, then they shifted the dark portion ahead by six hours. It took mice that have Tenm3 four days to adjust their circadian rhythm to the change. The mice without Tenm3 were able to adjust in about half the time. When the scientists did a similar experiment with light twice as dim, it took the mice with Tenm3 eight days to adjust their circadian rhythm, but it only took four days for mice without Tenm3. This suggests that Tenm3 helps the brain to sustain stable circadian rhythms even when light exposure is varied, such as a day when clouds float by and obscure the sun. By learning more about the role Tenm3 plays, researcher hope to treat conditions that lead to insomnia or even develop treatments for jet lag.
The implications of these findings from UC Berkeley and Johns Hopkins University extend far beyond mere academic curiosity. Insights gained from studying the evolution of the retina and the intricate connections within the visual system offer valuable information for addressing human eye diseases like glaucoma. Likewise, unraveling the molecular mechanisms underpinning circadian rhythms opens the door to innovative therapies for sleep disorders and related conditions. As research continues to uncover the mechanisms of these fundamental biological processes, we move closer to harnessing their full potential to enhance human health.
Sources:
https://news.berkeley.edu/2023/12/13/cell-types-in-the-eye-have-ancient-evolutionary-origins
https://www.nigms.nih.gov/education/fact-sheets/Pages/circadian-rhythms.aspx