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The key to the molecular switch was the ebb and flow of the thyroid hormone
Research

Retinas grown in lab to study colour vision

03/12/2018
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Biologists at Johns Hopkins University have grown retinas from scratch to determine how cells form to allow human colour vision.

The work, set for publication in the journal Science, lays the foundation to develop therapies for eye diseases such as colour blindness and macular degeneration.

The lab, led by developmental biologist Assistant Professor Robert Johnston, grew a retina in a dish before exploring “how a cell’s fate is determined”. According to the researchers, the growth replicates what happens in the womb to turn a developing cell into a specific type of cell, an aspect of human biology that is largely unknown.

Research focused on cells that allowed 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 colour vision of humans.

Johnston’s team overcame this by creating the human eyes they needed with stem cells.

“Everything we examine looks like a normal developing eye, just growing in a dish. You have a model system that you can manipulate without studying humans directly,” Johnston said.

Over several months, as the cells grew to become fully-fledged retinas, researchers found the blue-detecting cells materialised first, followed by the red and green-detecting cells.

In both cases, they discovered the key to the molecular switch was the ebb and flow of the thyroid hormone. Importantly, the level of this hormone wasn’t controlled by the thyroid gland, which isn’t in the dish, but entirely by the eye itself.

Johnston said by understanding how the amount of thyroid hormone dictated whether the cells became blue or red and green, the team could then manipulate the outcome. They created retinas that, if they were part of a complete human eye, would only see blue, green or red independently.

Lead author Ms Kiara Eldred, a Johns Hopkins graduate student, said discovering the link between the thyroid hormone and creating red-green cones explained why pre-term babies, who have lowered thyroid hormone levels due to a lack of maternal supply, have higher incidence of vision disorders.

“If we can answer what leads a cell to its terminal fate, we are closer to being able to restore colour vision for people who have damaged photoreceptors,” Eldred said.

The findings are just the first step for the lab. One day the research team wants to use organoids to learn more about colour vision and the mechanisms involved in creating other regions of the retina, such as the macula.

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With macular degeneration being a leading cause of blindness, Johnston said understanding how to grow a new macula could lead to clinical treatments.

“What’s exciting about this is our work establishes human organoids as a model system to study mechanisms of human development,” Johnston said.

“What’s really pushing the limit here is that these organoids take nine months to develop just like a human baby. So what we’re really studying is foetal development.

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