Biologists at Johns Hopkins University have discovered that thyroid hormone level dictates whether stem cells become blue, or green and red light-detecting cells as our eyes develop, and this shift is controlled by specific genes in our DNA.
The retina contains 3 types of colour sensing cells, commonly called "cones" because of their shape. By altering the amount of thyroid hormone that the cells had access to in the nutrient jelly that they grow on, the team were able to develop cones from stem cells that were only able to detect blue light, or only red and green.
Scientists already knew that the blue cones develop first in the eye, followed by the red and green. Now the team at Johns Hopkins have shown this also happens in their cells, demonstrating that the cells themselves control how much thyroid hormone they pick up when it is always present, as it would be in the body, and they do it by activating specific genes in sequence.
"What we did next was we grew these cells again, and we looked at the function of every gene, whether they were on or off," said senior author, Professor Robert Johnston. "What we found was early on, they [the active genes] degrade the thyroid hormone, and later there were different genes that were there to activate the thyroid hormone."
Premature babies can suffer from eye impairments due to the under-development of, or total absence of, these red and green cones. While it's still early, the team say that their findings could be used to generate potential targeted hormone treatments for these premature babies. What's more, they also say this research could also lead to treatments for the leading cause of vision loss in later life - macular degeneration:
“The challenge in studying this has been that mice, and fish, and the commonly used and very powerful model organisms don’t have this [macula] structure,” explains Johnston. Nor do they have any red cones at all, few mammals other than humans do!
“What we’re hoping is that by studying this in this developing human tissue model is that we can provide some insight into the development of the macula and down the line use our findings to provide therapy for this disorder.”
The macula is a small part of the retina, responsible for about 50% of your vision. A combination of factors can cause damage to the macula, some genetic and some environmental, such as smoking and lack of exercise, leading to the loss of central vision.
So, where next? One of the next targets of this research is to determine how the cones that become both red and green actually decide whether to be either red, or green. The team hope that further study of this stem cell development will yield answers as to whether this is random, or there is a driving influence there too.
But none of this is a speedy process. Each small collection of retinal cells, or “organoids” as these mini organ representatives are known, takes 6 - 12 months of attentive care, as they develop in the same timescale as they would in a growing foetus. So as Johnston explains, the work was a group effort:
“The team from my lab, including lead author Kiara Eldred, and co-authors Sarah Hadyniak and Kasia Hussey, are a fantastic group and it’s a privilege to be a mentor to them. It takes a special kind of person to do experiments that take 9 months to do, these scientists are both mentally tough and super smart. This work also couldn’t have happened without the help from Donald Zack and Karl Wahlin. It was perhaps a little too risky for some grants, but a special thank you to the Pew Foundation, they are known for funding high-risk, high-reward research.”