The lab grown retina that reveals the secret of how we see in color

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A closeup of 291 day old human eye tissue researchers grew in the lab: Biologists at Johns Hopkins University grew the human retinas from scratch to determine how cells that allow people to see in color are made


Researchers have grown human retinas from scratch using stem cells in a radical experiment that reveals how we see in color.

The biologists at Johns Hopkins University wanted to determine how cells that allow people to see in color are made. 

The study, in the journal Science, could lead to radical new therapies for eye diseases such as color blindness and macular degeneration. 

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A closeup of 291 day old human eye tissue researchers grew in the lab: Biologists at Johns Hopkins University grew the human retinas from scratch to determine how cells that allow people to see in color are made

The researchers say their groundbreaking study could lead to new ways to study the human body.

‘Everything we examine looks like a normal developing eye, just growing in a dish,’ said Robert Johnston, a developmental biologist at Johns Hopkins. 

‘You have a model system that you can manipulate without studying humans directly.’

Most vision research is done on mice and fish, but neither has the dynamic daytime and color vision of humans.

So Johnston’s team created the human eye tissue they needed – with stem cells. 

The team focused on the cells that allow people to see blue, red and green—the three cone photoreceptors in the human eye. 

‘Trichromatic color vision differentiates us from most other mammals,’ said lead author Kiara Eldred, a Johns Hopkins graduate student.

‘Our research is really trying to figure out what pathways these cells take to give us that special color vision.’

Over months, as the cells grew in the lab and became full-blown retina tissue, the team found the blue-detecting cells materialized first, followed by the red- and green-detecting ones. 

In both cases, they found the key was the ebb and flow of thyroid hormone.

The level of this hormone wasn’t controlled by the thyroid gland, which of course isn’t in the dish, but entirely by the eye itself.

Biologists at Johns Hopkins University grew human retinas from scratch to determine how cells that allow people to see in color are made.

Biologists at Johns Hopkins University grew human retinas from scratch to determine how cells that allow people to see in color are made.

The team focused on the cells that allow people to see blue, red and green¿the three cone photoreceptors in the human eye.

The team focused on the cells that allow people to see blue, red and green—the three cone photoreceptors in the human eye.

The researchers say their groundbreaking study could lead to new ways to study the human body. 

The researchers say their groundbreaking study could lead to new ways to study the human body. 

Understanding how the amount of thyroid hormone dictated whether the cells became blue or red and green receptors, the team was able to manipulate the outcome, creating retinas that if they were part of a complete human eye would only see blue, and ones that could only detect green and red.

This is a huge insight into why pre-term babies, who have lowered thyroid hormone levels as they are lacking the maternal supply, have a 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 color vision for people who have damaged photoreceptors,’ Eldred said. 

‘This is a really beautiful question, both visually and intellectually—what is it that allows us to see color?’

Inside the human eye: The biologists at Johns Hopkins University wanted to determine how cells that allow people to see in color are made

Inside the human eye: The biologists at Johns Hopkins University wanted to determine how cells that allow people to see in color are made

These findings are a first step for the lab. 

In the future, the researchers would like to use organoids to learn even more about color vision and the mechanisms involved in the creation of other regions 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 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 fetal development.’

WHAT IS CRISPR-CAS9?

CRISPR-Cas9 is a tool for making precise edits in DNA, discovered in bacteria.

The acronym stands for ‘Clustered Regularly Inter-Spaced Palindromic Repeats’.

The technique involves a DNA cutting enzyme and a small tag which tells the enzyme where to cut.

The CRISPR/Cas9 technique uses tags which identify the location of the mutation, and an enzyme, which acts as tiny scissors, to cut DNA in a precise place, allowing small portions of a gene to be removed

The CRISPR/Cas9 technique uses tags which identify the location of the mutation, and an enzyme, which acts as tiny scissors, to cut DNA in a precise place, allowing small portions of a gene to be removed

By editing this tag, scientists are able to target the enzyme to specific regions of DNA and make precise cuts, wherever they like.

It has been used to ‘silence’ genes – effectively switching them off.

When cellular machinery repairs the DNA break, it removes a small snip of DNA.

In this way, researchers can precisely turn off specific genes in the genome.

The approach has been used previously to edit the HBB gene responsible for a condition called β-thalassaemia. 

 



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