The human eye begins developing its ability to see fine details long before a baby is born. However, scientists have spent decades trying to understand exactly how the eye forms the specialized structures responsible for sharp central vision.
New research from Johns Hopkins University has uncovered an unexpected part of that process, revealing how a vitamin A derivative and thyroid hormones work together to shape the developing retina.
Published in the journal Proceedings of the National Academy of Sciences, the study challenges a scientific explanation that has guided vision research for approximately 30 years. The findings suggest that some light-detecting cells in the developing eye do not simply move to different locations as the retina forms. Instead, they may change their identities as development progresses.
The discovery offers a closer look at how human color vision develops and could eventually help researchers investigate ways to restore sight damaged by retinal diseases.
Scientists Investigated the Part of the Eye Responsible for Sharp Vision
The research focused on the foveola, a tiny region located at the very center of the retina. The retina is the light-sensitive layer at the back of the eye that converts incoming light into signals the brain can interpret.
Although the foveola occupies only a small portion of the retina, it plays an important role in detailed central vision. It helps people perform everyday activities that require distinguishing fine details, including reading, recognizing faces, and identifying objects.
According to the researchers, this small region is involved in approximately 50% of human visual perception.
Understanding how the foveola develops has been particularly challenging because commonly studied animals, including mice and fish, do not have the same retinal organization as humans. This makes it difficult for scientists to rely on traditional animal experiments when investigating the development of specialized human vision.
To overcome this limitation, researchers used miniature human retinal tissues grown in the laboratory.
Miniature Human Retinas Revealed Changes Before Birth
The team, led by Robert J. Johnston Jr., an associate professor of biology at Johns Hopkins University, studied retinal organoids. These are small, laboratory-grown clusters of cells that reproduce important features of developing human retinal tissue.
By observing the organoids over several months, the researchers could follow changes that would otherwise be difficult to examine during pregnancy.
Their investigation focused on specialized light-detecting cells called cones. Unlike rod cells, which are particularly important for vision in dim lighting, cones support daytime vision and allow people to distinguish colors.
Humans have three types of cones, commonly described as blue, green, and red cones. Each type responds most strongly to different wavelengths of light, allowing the brain to interpret a broad range of colors.
However, these cells are not distributed evenly across the retina. The foveola contains red and green cones but lacks blue cones, a particular arrangement associated with its ability to support exceptionally sharp central vision.
The researchers wanted to understand how the developing eye establishes this specific pattern.
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Vitamin A Helps Determine Which Cells Develop in the Retina
The study identified retinoic acid, a molecule produced from vitamin A, as an important influence on the development of the foveola.
Retinoic acid helps regulate how cells grow and specialize in different parts of the body. In the developing retina, the researchers found that the breakdown of this molecule helps limit the formation of blue cones in the central region.
However, its role appears to be only part of the process.
The researchers observed that between weeks 10 and 12 of fetal development, a small number of blue cones were initially present in the foveola. By week 14, these cells appeared to have transformed into red and green cones.
This observation pointed to another important influence: thyroid hormones.
Although thyroid hormones are widely recognized for their role in regulating metabolism, they also contribute to growth and development. In the developing retina, they appear to encourage the remaining blue cones to change into red and green cones.
Together, these two chemical influences help establish the specialized arrangement of cone cells in the center of the retina.
Importantly, the findings concern vitamin A signaling during early eye development. They do not demonstrate that taking vitamin A supplements can improve eyesight in adults.
The Discovery Challenges a Theory Scientists Have Held for Decades
For approximately 30 years, researchers have worked with a different explanation for why the foveola lacks blue cones.
The longstanding theory suggested that blue cones initially present in the developing central retina gradually moved away as the eye matured. It also assumed that once a cone cell developed a particular identity, it retained that identity rather than changing into another type.
The new research offers a different possibility.
Instead of simply relocating, some blue cones may actually change into red and green cones during fetal development. This suggests that developing retinal cells have more flexibility than scientists previously understood.
The researchers have not completely ruled out the possibility that some cells also migrate. However, their observations support the idea that changes in cell identity contribute to the formation of the foveola.
This distinction matters because understanding how cells acquire their specialized functions could help scientists better explain how human color vision develops.
It also provides a new direction for investigating the biological processes responsible for the retina’s highly specialized structure.
Could the Findings Eventually Help Restore Lost Vision?
Beyond explaining how healthy eyes develop, the research could have implications for future treatments involving retinal damage.
One condition of particular interest is macular degeneration, which damages the macula, the region of the retina responsible for detailed central vision. The condition can make activities such as reading, driving, and recognizing faces increasingly difficult, particularly among older adults.
Although certain treatments can slow or manage some forms of the disease, there is currently no cure.
The researchers believe that understanding how specialized retinal cells develop could eventually help them produce replacement cells in the laboratory.
Johnston’s team is working to improve its retinal organoids so they more closely reproduce the structure and function of the human eye. The longer-term goal is to create carefully controlled populations of photoreceptors, the cells responsible for detecting light, for potential transplantation into damaged retinas.
Katarzyna Hussey, a study author and former doctoral student in Johnston’s laboratory, described cell replacement therapy as a potential direction for this technology. She is now a molecular and cell biologist at CiRC Biosciences, a cell therapy company in Chicago.
However, this approach is still experimental. Scientists would need to establish that transplanted cells can survive, connect properly with existing retinal tissue, and function safely before such treatments could be considered for clinical use.
Extensive safety and effectiveness testing would also be necessary.
For now, the discovery provides a more detailed explanation of how the human eye develops its ability to see fine details. By identifying the roles of retinoic acid and thyroid hormones, researchers have uncovered another important part of the biological process that makes sharp human vision possible.
Did you know that the human eye undergoes such complex changes before birth, and what surprised you most about these findings?
