Kiara Eldred sometimes compares her nine-month scientific experiments, the cultivation of small human retinas in a laboratory dish, the raising of children.
Eldred, a graduate student at Johns Hopkins University, starts growing thousands of stem cells and feeding nutrients and chemicals that will send them to develop into the retina, the part of the eye that translates light into the signals that go to to lead the view. After two weeks of painstaking cultivation, these cells usually produce 20 to 60 small balls of cells called retinal organoids. As they get older, these emerging retinas become dirty and rotate a lot of cells, so they also have to be washed off when they are fed every other day – at least for the first month and a half.
After nine months of careful care, Eldred has a batch of miniature human retinas that respond to light, about two millimeters in diameter and have the shape of a tennis ball cut in half. But letting the organoids grow is only the first step.
In a new study in the magazine Science, Eldred and colleagues described this system to understand a fundamental question about vision that has remained surprisingly mysterious: how does a color vision develop?
The researchers discovered that the blue cone cells, which detect blue light, first develop and that the red and green photoreceptor cells start to develop later. They also found that thyroid hormone appears to be the critical signal in determining which light-detecting cells are developing.
Ultimately, the researchers hope that the insights can help to develop treatments for diseases in which these light-detecting cells are depleted, such as macular degeneration. A better understanding of the process can lead to therapies for eye disorders that develop in premature babies.
"The ideal goal would be to take a person's cells, convert them into stem cells, and then re-program and place them back in the person and treat whatever the disease is," said Robert Johnston Jr., a developmental neurobiologist at Johns Hopkins, who leads the lab where Eldred works.
But organoids have limitations. Human retinas are about 15 times larger than the organoids, which are about the size of the inner ring of a piece of Cheerios grains, according to Eldred. There are still plenty of questions about how well they reflect eye development in the fetus because they lack many other peripheral structures. But the ability to grow these organoids in a scale on a time scale that reflects human development offers a rare window to questions that otherwise would not be easy to gauge.
"If in the past we wanted to develop the development mechanisms that underlie a particular process, we would turn to model organisms such as mice or zebrafish," said Thomas Reh, a scientist at the University of Washington who studies the development of the eye. Reh, who was not involved in the study, called it "really excellent basic biology."
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