Johns Hopkins University
To see the red of a sunset or the green of the spring leaves, developing human eyes need to get the right hormone at the right time.
This is the result of a group of scientists who have studied how color vision is developed using hundreds of human retinas grown in the laboratory.
The discovery, published Thursday in the journal Science could help accelerate current efforts to treat color blindness. It could also lead to new treatments for diseases such as macular degeneration, the leading cause of vision loss
"It is important to understand how nature controls the development of the retina so you can better understand why things go wrong in the disease and how we can treat them, "says Steven Becker, a National Eye Institute scientist. The results just published are a step in this direction, says Becker, who has no connection with the research.
The development of color vision in people has been difficult to study because it usually occurs in the uterus – and out of sight. But two Johns Hopkins University scientists thought they could find answers using laboratory-grown retinas.
These "retinal organoids" have been around for some years, but they are difficult and tedious to grow, says Kiara Eldred, a Hopkins graduate student who is the first author of the paper.
It takes a year to transform a series of immature retinal cells into a functioning organoid.
"For the first week of their lives, I take care of them every day," says Eldred. After a couple of weeks, he says, the cells become "a little more independent".
And fortunately, these groups of immature cells develop into a 3D structure that "looks and acts like a developing retina you would see in a child," says Bob Johnston, Eldred's chief and assistant professor in the department of biology.
Johnston's lab had studied vision in flies. But he and Eldred saw the possibility of trying something much more ambitious.
"We discussed this crazy idea of being able to use these human retinal organoids to study how we get the different cells that perceive color in our eyes," says Johnston.
The use of human cells has been crucial because it is not possible to study how humans see color in a fly or even in a mouse.
"Mice do not perceive red," says Johnston. "They do not have these cells that detect red, so we really have to study it in human tissue to get an idea of how it works."
Johnston and Eldred knew that in a human fetus, the cells that detect blue light appear first Then the cells that respond to red and green light arrive.
And animal research has suggested that thyroid hormone be involved in the development of these color-sensitive cells, called cones. So Johnston had Eldred perform an experiment with immature retinal cells.
"I added thyroid hormone to the dish during their development and we developed more red-green cones in these organoids," he says. "We really got excited because we were doing something."
It would take years and many other experiments to confirm that the thyroid hormone was actually triggering the emergence of color vision. And the team has not yet figured out what causes some cones to become even more specialized by detecting only red or green.
But Johnston says his lab is preparing to take on two new goals.
"One is to restore color vision to people who are colorblind," he says. What his lab is learning, he says, could help accelerate an existing effort to use gene therapy to treat color blindness.
The second objective of the laboratory is to use retinal organoids to better understand diseases including glaucoma and macular degeneration, one of the main causes of loss of vision .
Macular degeneration affects the macula, an area of the retina that provides a high-resolution vision. The condition has been difficult to study, however, because mice do not have a macula.
So Johnston hopes to learn more by having his lab create macular organoids.
There is growing optimism among scientists that new treatments for retinal diseases will emerge from such efforts, says Becker. Initially, he says, the researchers doubted that a retina raised in a dish could mimic the real thing.
But studies like this on color vision, he says, "show that the resemblance is quite high."
To encourage scientists to develop more retinal organoids, the National Eye Institute sponsors a scientific competition with $ 1 million in prizes.