Lab-Grown Human Retinas Reveal Keys to Color Vision

"My co-authors and I all kind of refer to them as our babies."

In a lab at Johns Hopkins University, little bits of human eyes are growing in a dish. While growing eye globs is a technical marvel in itself, this creation has a compounded purpose. In a new study published in the journal Science, scientists generated these organoids to understand why we can see color and to learn how to help people who can’t.

When one thinks of an eye, they likely think of the full, bulbous form — the lens, an iris; the vitreous body. These retinal organoids are not that. Technically, they’re retinas grown from human stem cells — globs of the white tissue that lines the very back of the eye.

In the study, published Thursday, Johns Hopkins University graduate student Kiara Eldred and her team reveal why these retinas are so important. Humans have three types of color-detecting cells, cone-shaped photoreceptors that sense red, green, or blue light. But the mechanisms behind why this is haven’t been fully understood. Here, the team discovered that blue cells develop first, then red and green cells later. Learning the timing of these cell formations was a novel finding — and made sense, considering we and other primates have something called trichromatic color vision.

“As a scientist, I think that you have to have a passion for what you’re doing and a connection to your organism,” organoid-creator Eldred tells Inverse. “I cared for the organoids every day in the beginning and then every other day as they got older. In the lab, my co-authors and I all kind of refer to them as our babies because we have to care for them all the time.”

A retina organoid in its dish.

Johns Hopkins University

“Most mammals can only see in two spectrums of color — they only see blue and green,” Eldred explains. “We can see blue, green, and red. Because of color vision we’re able to receive a lot of rich information about the world around us.”

It’s speculated that primates like chimps and humans can see red because the ability enabled early hominins to find ripening fruit among green leaf backgrounds. Meanwhile, other mammals like dogs and cats see fewer and weaker colors.

The realization that something was prompting the timing of the blue, red, and green cell growth also posed a mystery: What mechanism caused the creation of these three types of cone cells? To figure it out, after directing stem cells to become retinal tissue — a process in which sometimes the scientists end up creating brain tissue as well as the retinal tissue because, after all, photoreceptors are technically neurons — the researchers began to test a set of genes involved in the function of the thyroid hormone, which is involved in cell growth and differentiation.

Previous work concerning mice, fish, and chicken vision suggested that when thyroid hormone function is low, blue cells emerge, and when it’s high, red and green cells follow. That turned out to be true: Using CRISPR, researchers knocked out the receptor for the thyroid hormone and created retina organoids with only blue cells. When they added the hormone back in, they generated organoids with only red and green cells.

Stem cells are directed to become retinas in a dish.

Johns Hopkins University

This was happening even though the thyroid gland wasn’t involved at all — the only items in the dish were the retina organoids. After examining what genes turned on or off during a year of organoid development, they discovered their hypothesis was correct: Genes that degrade the thyroid hormone were on early to make the blue cells, and genes that activate the thyroid hormone were on later to create red and green cells.

Essentially the scientists were causing the organoids to become color blind in different ways. This suggests that this research could be useful in developing therapeutic treatments to help people who are color blind or suffer from macular degeneration, an eye disease that causes vision loss. Currently, what scientists do to help with macular degeneration is inject stem cells into retinas that have some kind of degeneration. However, the efficacy of this process has been unpredictable. The goal now is that, by being able to direct the path of differentiation of the cone cells, scientists can learn how they can use the cells therapeutically.

“We’re hoping that with our research, we can provide information to other researchers on how to create cone cells specifically,” says Eldred. “In future experiments we can perhaps take these cells, inject them, and more of them will become photoreceptors that can actually provide regenerative treatment. Every time I see the organoids going down the correct path, it’s exciting and fascinating.”

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