Developmental biology - Vision|
How Color Vision Develops
Growing human retinas from scratch reveals how cells see in color...
New work published in the journal Science, lays the foundation for therapies in eye diseases such as color blindness and macular degeneration. It also establishes how lab-created "eye organoids" model development of our human eye on the cellular level.
"Everything we examine looks like a normal developing eye, just one growing in a dish. You have a model system that you can manipulate without studying humans directly."
Robert J. Johnston Jr. PhD, Department of Biology, Johns Hopkins University, Baltimore, Maryland, USA.
Johnston's lab explores how a cell's fate is determined - or what exactly happens in the womb to turn a developing cell into a specific cell type, an aspect of human biology that is largely unknown.
Here, he and his team focused on the cells that allow people to see blue, red and green - the three cone photoreceptors in the human eye.
While most vision research is done on mice and fish, neither of those species has the dynamic daytime and color vision of humans. So Johnston's team created the human eyes they needed - using stem cells. "Trichromatic color vision delineates us from most other mammals," said lead author Kiara Eldred, a Johns Hopkins graduate student. "Our research is really trying to figure out what pathways these cells take to give us that special color vision."
Understanding how the amount of thyroid hormone dictates whether cells became blue, or red and green, scientists were able to manipulate cell outcomes, creating retinas that - if they were actually part of a complete human eye - would only see blue, and ones that would only see green and red. That thyroid hormone is essential in creating red-green cones provides insight into why premature babies having lower thyroid hormone levels, as they lack a full maternal supply, have high incidences of vision disorders.
Over months, as the cells grew in the lab and became full-blown retinas, the team found the blue detecting cells materialize first, followed by red and green detecting cells. In both cases, the molecular switch was the ebb and flow of thyroid hormone. Specifically, the level of thyroid hormone isn't controlled by the thyroid gland as it isn't in the petri dish, but entirely by the eye itself.
Understanding the amount of thyroid hormone dictates when cells became blue or red and green, the team was able to manipulate outcomes, creating retinas that if they were part of a complete human eye, that eye would only see blue, or, could only see green and red.
"If we can answer what leads a cell to its terminal fate, we are closer to being able to restore color vision for people who have damaged photoreceptors," Eldred adds. "This is a really beautiful question, both visually and intellectually - what is it that allows us to see color?"
These findings are a first step for the lab. In the future they would like to use organoids to learn even more about color vision and the mechanisms involved in the creation of other regions of the retina, such as the macula. Since macular degeneration is one of the leading causes of blindness, knowing how to grow a new macula could lead to clinical treatments.
"What's exciting is our work establishes human organoids as a model system to study mechanisms of human development. What's really pushing the limit — these organoids take nine months to develop just like a human baby. So we are really studying fetal development."
Robert J. Johnston Jr. PhD
Cone photoreceptors in the human retina enable daytime, color, and high-acuity vision. The three subtypes of human cones are defined by the visual pigment that they express: blue-opsin (short wavelength; S), green-opsin (medium wavelength; M), or red-opsin (long wavelength; L). Mutations that affect opsin expression or function cause various forms of color blindness and retinal degeneration.
Our current understanding of the vertebrate eye has been derived primarily from the study of model organisms. We studied the human retina to understand the developmental mechanisms that generate the mosaic of mutually exclusive cone subtypes. Specification of human cones occurs in a two-step process. First, a decision occurs between S versus L/M cone fates. If the L/M fate is chosen, a subsequent choice is made between expression of L- or M-opsin. To determine the mechanism that controls the first decision between S and L/M cone fates, we studied human retinal organoids derived from stem cells.
Kiara C. Eldred, Sarah E. Hadyniak, Katarzyna A. Hussey, Boris Brenerman, Ping-Wu Zhang, Xitiz Chamling, Valentin M. Sluch, Derek S. Welsbie, Samer Hattar, James Taylor, Karl Wahlin, Donald J. Zack, Robert J. Johnston Jr.
The research team also included Sarah Hadyniak, Katarzyna Hussey and Boris Brenerman, Johns Hopkins University graduate students; Ping-Wu Zhang, Xitiz Chamling and Valentin Sluch, researchers at the Wilmer Eye Institute; Derek Welsbie of the Shiley Eye Institute; Samer Hattar, a professor at the NIH; James Taylor, a Johns Hopkins professor of biology and computer science; Karl Wahlin of the Shiley Eye Institute, and Donald Zack, a professor in the university's School of Medicine.
The work is funded by the National Institutes of Health (R00 HD073239), the W.M. Keck Foundation and a Pew Biomedical Scholars Award.
This work was funded by the Pew Charitable Trusts grant 00027373, the Howard Hughes Medical Institute, the National Science Foundation grant 1746891, and the National Institutes of Health.
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Oct 17, 2018 Fetal Timeline Maternal Timeline News News Archive
A fully developed and functioning human retina. Photo by R J Johnston PhD, Johns Hopkins University