Vitamin A molecule helps shape sharp central vision before birth, lab finds

Scientists at Johns Hopkins University report that a molecule made from vitamin A helps shape the part of the human eye used for the sharpest sight, working together with thyroid hormone before birth.¹ The study, published in the journal Proceedings of the National Academy of Sciences, was done in miniature human retinas grown in the lab, not in people.¹ The researchers say the findings challenge an explanation of how this part of the eye forms that has stood for roughly 30 years.¹

What the researchers found

The study focused on the foveola, a tiny spot at the very center of the retina, the light-sensitive layer at the back of the eye.¹ The foveola handles detailed central vision, the kind people use to read, recognize faces and see fine details.² It takes up only a small fraction of the retina, but the researchers say it is involved in about half of human visual perception.¹

Color and daytime vision depend on cells called cones. Humans have three kinds, usually described as blue, green and red cones, each most sensitive to a different range of light.¹ Most of the retina has all three, but the foveola has red and green cones and no blue ones, an arrangement described as essential for the sharp vision at the center of the eye.¹

The team reports that this pattern forms in two steps. During weeks 10 to 12 of fetal development, a small number of blue cones are present in the foveola. By week 14, these cells appear to have turned into red and green cones.¹ The researchers name two chemical signals behind this:

• Retinoic acid, a molecule the body makes from vitamin A, which helps steer how cells develop and specialize. In the developing retina, it is linked to limiting how many blue cones form in the center.²
• Thyroid hormone, best known for controlling metabolism, which appears to push the remaining blue cones to change into red and green cones.¹

“First, retinoic acid helps set the pattern. Then, thyroid hormone plays a role in converting the leftover cells,” Johnston said.

¹

The accounts differ slightly on one detail. The Johns Hopkins release says it is the breakdown of retinoic acid in the developing retina that limits blue cones in the center,¹ while two news reports describe retinoic acid itself as limiting them.³² The paper itself was not among the sources Biohack reviewed, so this point could not be checked against it.

How the study was done

The scientists did not rely mainly on animals, because commonly studied animals such as mice and fish do not have the same retinal layout as humans.¹ Instead, they grew organoids: small clusters of human cells that form miniature versions of retinal tissue and copy important features of a developing eye.¹ The team has helped develop this technique over the past several years.¹

By watching the organoids over several months, the researchers could follow changes that would otherwise be extremely hard to study during pregnancy.¹

The study was led by Robert J. Johnston Jr., an associate professor of biology at Johns Hopkins.¹ He called it “a key step toward understanding the inner workings of the center of the retina, a critical part of the eye and the first to fail in people with macular degeneration.”¹

The older explanation it challenges

For decades, a leading explanation held that blue cones in the developing foveola simply moved away to other parts of the retina while staying blue cones.² The new observations suggest instead that some of these cells change their identity as the eye develops.²

The researchers have not fully ruled out that some cells also move. Their findings support an alternative explanation rather than closing the question.²

What it does not show yet

This is lab dish work. Organoids reproduce important features of developing human tissue,¹ but they are not a whole eye inside a growing baby. What the cells appear to do in a dish still has to be squared with what happens in a real pregnancy.

The study also says nothing about diet or pills. The researchers stressed that the discovery concerns vitamin A signaling during fetal development and does not mean that taking vitamin A supplements can improve vision in adults.²

No treatment has come out of this work. Links to diseases such as macular degeneration and glaucoma are described as possible future directions for research,¹ not results.

Who is behind it

The work comes from Johnston’s lab at Johns Hopkins University.¹ One co-author, Katarzyna Hussey, is a former doctoral student in that lab and now works as a molecular and cell biologist at CiRC Biosciences, a Chicago-based cell therapy company.² The sources Biohack reviewed did not describe who funded the study.

Hussey said the long-term goal is cell replacement therapy, putting healthy light-sensing cells back into damaged eyes.

“The goal with using this organoid tech is to eventually make an almost made-to-order population of photoreceptors. A big avenue of potential is cell replacement therapy to introduce healthy cells that can reintegrate into the eye and potentially restore that lost vision,” she stated.

³

She also cautioned that the technology is at an early stage and needs extensive development, safety checks and effectiveness testing before it could be considered for use in patients.²

How it fits the field

Macular degeneration damages the central part of the retina and can seriously affect reading, driving and recognizing faces. Some treatments can slow it, but there is no cure.² Because the center of the retina is the first part to fail in this disease,¹ knowing how it is built in the first place matters to researchers who want to rebuild it.

Johnston’s team is working to make its lab-grown retinas more closely match the structure and function of the human eye. The long-term aim is to produce photoreceptors, the light-detecting cells, that could one day be transplanted into damaged retinas.² Johnston said the team hopes “to one day grow and transplant these tissues to restore vision.”¹

Understanding which signals turn a cell into a red, green or blue cone could, in principle, help scientists steer lab-grown cells toward the kinds the center of the eye needs. That is a hope stated by the researchers, not something this study tested.

What to watch next

• Whether other labs see the same blue-to-red-and-green change in their own retinal organoids or in human eye tissue.
• Whether the open question of cell movement versus cells changing identity gets settled.²
• Progress on organoids that better mimic the human eye, and any move toward producing photoreceptors for transplant, which would require safety and effectiveness testing first.²