Studying Color Vision in a Dish

Posted on December 13th, 2018 by Dr. Francis Collins

Credit: Eldred et al., Science

Researchers can now grow miniature versions of the human retina—the light-sensitive tissue at the back of the eye—right in a lab dish. While most “retina-in-a-dish” research is focused on finding cures for potentially blinding diseases, these organoids are also providing new insights into color vision.

Our ability to view the world in all of its rich and varied colors starts with the retina’s light-absorbing cone cells. In this image of a retinal organoid, you see cone cells (blue and green). Those labelled with blue produce a visual pigment that allows us to see the color blue, while those labelled green make visual pigments that let us see green or red. The cells that are labeled with red show the highly sensitive rod cells, which aren’t involved in color vision, but are very important for detecting motion and seeing at night.

Researchers recently discovered that in retinal organoids, just like in the developing human retina, the blue-detecting cone cells are the first to appear. Next come the green or red-detecting cone cells. The brain then processes these visual signals in a full spectrum of color.

Previous work in animals had indicated that the retina’s development may depend on hormonal signals from an organ that we don’t usually associate with vision: the thyroid. How could that be? Researchers in the lab of Robert Johnston Jr. at Johns Hopkins University, Baltimore, turned to retinal organoids for a closer look.

As published recently in the journal Science [1], the Hopkins team, led by Kiara Eldred, determined that retinal tissue actually degrades thyroid hormone early in development. That allows production of the blue-detecting cone cells. They went on to discover that, later in development, retinal tissue does exactly the opposite: it actually activates thyroid hormone to stimulate production of red or green-detecting cells.

When the researchers created retinal organoids that lacked receptors for thyroid hormone, those organoids produced only blue-detecting cone cells. In other words, these retinas-in-a-dish suffered from red-green color blindness!

As is the case for many other types of organoids, creating a retina-in-a-dish is no simple task. After coaxing induced pluripotent stem (iPS) cells derived from mature human skin cells to differentiate into retinal organoids, each about the size of a pinhead, Eldred and her colleagues tend them carefully to keep them alive and well. In fact, they report that they now have some retinal organoids that are 500 days old.

The Hopkins researchers have found that their retinal organoids develop much as a retina would in a living human. While the cells aren’t packed quite as orderly as in the real thing, all of the cell types are there and they even show similar patterns of gene activity.

Most of our current understanding of vision comes from studies conducted in animals. However, mice and many other animals don’t view colors like we do, which has made it very difficult to answer some important questions about human color vision. But the emergence of organoid technology is helping to provide a way around those limitations, and that’s a beautiful thing to see.

Reference:

[1] Thyroid hormone signaling specifies cone subtypes in human retinal organoids. Eldred KC, Hadyniak SE, Hussey KA, Brenerman B, Zhang PW, Chamling X, Sluch VM, Welsbie DS, Hattar S, Taylor J, Wahlin K, Zack DJ, Johnston RJ Jr. Science. 2018 Oct 12;362(6411).

Links:

Johnston Lab (Johns Hopkins University, Baltimore)

Video: Ask a Scientist—What is Colorblindness (National Eye Institute/NIH)

Stem Cell Basics (NIH)

Tissue Chip for Drug Screening (National Center for Advancing Translational Sciences/NIH)

NIH Support: National Eye Institute

https://nei.nih.gov/3DROC