Vitamin A & Thyroid Hormones Key to Sharp Human Vision Development
Scientists at Johns Hopkins University have discovered a surprising mechanism in early fetal development that dictates how humans achieve sharp, high-acuity vision. The research, published today in Proceedings of the National Academy of Sciences, reveals that the arrangement of light-sensing cells in the retina isn’t simply a matter of cell migration, as previously thought, but a coordinated process of cell conversion driven by a vitamin A derivative and thyroid hormones.
The findings could reshape understanding of how the eye develops and potentially inform new treatments for age-related vision disorders like macular degeneration and glaucoma, conditions for which there are currently no cures. “This is 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,” said Robert J. Johnston Jr., an associate professor of biology at Johns Hopkins who led the research.
For decades, scientists have puzzled over the unique structure of the human foveola – the central region of the retina responsible for approximately 50% of human visual perception. Unlike other animals commonly used in vision research, humans possess three types of cone cells – sensitive to blue, green, and red light – arranged in a specific pattern within the foveola. The foveola itself is densely populated with red and green cones, while blue cones are more broadly distributed across the rest of the retina. Mice, fish, and other organisms lack this specific patterning, making it difficult to study the photoreceptor cells, Johnston explained.
The Johns Hopkins team utilized a novel method of studying eye development using lab-grown retinal organoids – small tissue clusters grown from fetal cells. By monitoring these organoids over several months, researchers observed the cellular changes that shape the foveola. Their work focused on the development of cone cells, which enable daytime vision. Initially, a sparse number of blue cones are present in the foveola between weeks 10 and 12 of development. Yet, by week 14, these blue cones begin to transform into red and green cones.
The process unfolds in two distinct stages, according to the study. First, a molecule derived from vitamin A, known as retinoic acid, breaks down to limit the creation of new blue cones. Second, thyroid hormones encourage the existing blue cones to convert into red and green cones. “First, retinoic acid helps set the pattern. Then, thyroid hormone plays a role in converting the leftover cells. That’s very important because if you have those blue cones in there, you don’t see as well,” Johnston said.
This discovery challenges the long-held belief that blue cones simply migrate out of the foveola during development. “The main model in the field from about 30 years ago was that somehow the few blue cones you get in that region just move out of the way, that these cells decide what they’re going to be, and they remain this type of cell forever,” Johnston said. “We can’t really rule that out yet, but our data supports a different model. These cells actually convert over time, which is really surprising.”
Katarzyna Hussey, a former doctoral student in Johnston’s lab and now a molecular and cell biologist at CiRC Biosciences in Chicago, emphasized the potential for future therapies. “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,” Hussey said. Johnston and his team are continuing to refine their organoid models to better replicate human retina function, with the aim of developing improved photoreceptors for cell-based treatments. Further safety and efficacy studies are needed before any clinical trials can begin.