Vitamin A and Thyroid Hormones Work Together to Shape Human Sharp Vision Before Birth

At the center of each human retina sits a patch of tissue so small it is easy to overlook, yet the researchers who study it say it is involved in about 50 percent of visual perception. It is called the foveola, and a team at Johns Hopkins University has now worked out part of how it gets built before a baby is born.

The study, published in Proceedings of the National Academy of Sciences, was led by Robert J. Johnston Jr., an associate professor of biology at Johns Hopkins. His group did not rely on animal models. Mice and fish do not share the retinal organization humans have, which has long made the foveola hard to study. Instead, the team grew retinal organoids, miniature clusters of tissue grown from fetal cells that reproduce important features of developing human tissue. Watching them over several months let the scientists follow changes that would be extremely difficult to observe during pregnancy.

The puzzle centers on cones, the light-detecting cells that support daytime vision and color perception. Humans have three kinds, commonly described as blue, green and red, and the brain compares their signals to distinguish a wide range of colors. They are not spread evenly. The foveola contains red and green cones but no blue ones, and that arrangement is essential to the exceptionally sharp vision at the center of the eye. How the pattern arises has been unexplained for decades.

The organoids suggest two coordinated processes. Between weeks 10 and 12 of fetal development, a small number of blue cones are present in the foveola. By week 14, those cells appear to have become red and green cones. The first influence is retinoic acid, a molecule made from vitamin A that helps regulate how cells specialize. In the developing retina, its breakdown limits the formation of blue cones in the central region. The second is thyroid hormone, best known for regulating metabolism, which appears to push the remaining blue cones to convert.

"First, retinoic acid helps set the pattern. Then, thyroid hormone plays a role in converting the leftover cells," Johnston said. He added that the conversion matters because blue cones in that spot would mean worse vision.

The finding cuts against a model that has dominated the field for about 30 years. Under it, the few blue cones that appear in the foveola simply move out of the way, and each cell's identity is fixed once chosen. Johnston said the team cannot rule that out yet, but their data support a different picture in which cells convert over time, which he called really surprising. The researchers have not excluded the possibility that some cells migrate. The work does not show that vitamin A supplements could improve sharp vision in adults; it concerns signaling before birth.

The longer-term motivation is disease. Macular degeneration, a major cause of central vision loss especially in older adults, damages the macula and can interfere with reading, driving and recognizing faces. Treatments can slow or manage some forms, but there is no cure. Johnston calls the center of the retina the first part to fail in the condition, and says the hope is to one day grow and transplant tissues to restore vision. His team is now improving its organoids to better match the structure and function of the human eye, aiming for precisely controlled populations of photoreceptors.

Study author Katarzyna Hussey, a former doctoral student in Johnston's lab and now a molecular and cell biologist at CiRC Biosciences, a cell therapy company in Chicago, described the goal as an almost made-to-order supply of photoreceptors for cell replacement. Transplanted cells would have to survive, connect properly to the eye's existing circuitry and work safely. She stressed that these are very long-term experiments needing safety and efficacy studies before any clinic, but called it a viable journey. What to watch is whether the organoids can be refined enough to produce reliable, controlled photoreceptor populations.