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Johns Hopkins University biologists have developed the human retina from scratch to determine how cells allowing people to see in color are made.
The work, intended to be published in the journal Science, lays the foundation for the development of therapies for eye diseases such as color blindness and macular degeneration. He also establishes "organoids" created in the laboratory as a model for studying human development at the cellular level.
"Everything we look at looks like a normal developing eye, which grows in a dish," said Robert Johnston, development biologist at Johns Hopkins. "You have a model system that you can manipulate without directly studying humans."
Johnston's lab explores how the fate of a cell is determined – or what happens in the uterus to turn a developing cell into a specific type of cell, an aspect of human biology largely unknown.
Here, Johnston and his team focused on cells that allow people to see blue, red and green – the three-cone photoreceptors of the human eye.
Although most vision research focuses on mice and fish, none of these species possess the dynamic vision of the day and the colors of humans. Johnston's team created the human eyes she needed with stem cells.
"The trichromatic color vision sets us apart from most other mammals," said Kiara Eldred, lead author and graduate student of Johns Hopkins. "Our research is really trying to determine the paths taken by these cells to give us this particular color vision."
Over the months, as the cells grew into the lab and became full-fledged retinas, the team discovered that the blue-sensing cells materialized first, followed by the red and blue detection cells. green. In both cases, they discovered that the key to the molecular switch was the ebb and flow of the thyroid hormone. Importantly, the level of this hormone was not controlled by the thyroid gland, which, of course, is not in the dish, but entirely by the eye itself.
Understanding how the amount of thyroid hormones dictated whether the cells became blue, red, or green, the team was able to manipulate the result by creating retinas that, if they were part of a complete human eye, would only see from blue, and see green and red.
The discovery that thyroid hormones are essential for the creation of red-green cones helps to better understand why premature babies, whose thyroid hormone levels are low because they lack resources for the mother, have a higher incidence vision disorders.
"If we can determine what drives a cell to its ultimate fate, we will be closer to being able to restore color vision for people who have damaged photoreceptors," said Eldred. "It's a very beautiful question, both visually and intellectually – what allows us to see the colors?"
These results are a first step for the laboratory. In the future, they would like to use organoids to learn about color vision and the mechanisms involved in creating other areas of the retina, such as the macula.
Since macular degeneration is one of the leading causes of blindness in people, understanding how to grow a new macula could lead to clinical treatments.
"What's exciting is our work that establishes human organoids as a model system for studying the mechanisms of human development," said Johnston. "What really pushes the limit is that these organoids take nine months to develop as a human baby. So we are really studying fetal development. "
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