How did humans develop sharp vision? Lab-grown retinas show likely answer

(Press-News.org) Humans develop sharp vision during early fetal development thanks to an interplay between a vitamin A derivative and thyroid hormones in the retina, Johns Hopkins University scientists have found.  

The findings could upend decades of conventional understanding of how the eye grows light-sensing cells and could inform new research into treatments for macular degeneration, glaucoma, and other age-related vision disorders. 

Details of the study, which used lab-grown retinal tissue, are published today in Proceedings of the National Academy of Sciences.

“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. “By better understanding this region and developing organoids that mimic its function, we hope to one day grow and transplant these tissues to restore vision.” 

In recent years, the team pioneered a new method to study eye development using organoids, small tissue clusters grown from fetal cells. By monitoring these lab-grown retinas over several months, the researchers discovered the cellular mechanisms that shape the foveola—a central retinal region responsible for sharp vision. 

Their research focused on light-sensitive cells that enable daytime vision. These cells develop into blue, green, or red cone cells that have sensitivity to different types of light. Although the foveola comprises only a small fraction of the retina, it accounts for about 50% of human visual perception. The foveola contains red and green cones but not blue cones, which are distributed more broadly across the rest of the retina. 

Humans are unique in having these three types of cones for color vision, allowing people to see a wide spectrum of colors that are relatively rare in other animals. How eyes grow with this distribution of cells has puzzled scientists for decades. Mice, fish, and other organisms commonly used for biological research do not have this patterning of cells, which makes the photoreceptor cells difficult to study, Johnston said. 

The Johns Hopkins team concluded the distribution of cones in the foveola results from a coordinated process of cell fate specification and conversion during early development. Initially, a sparse number of blue cones are present in the foveola at weeks 10 through 12. But, by week 14, they transform into red and green cones. The patterning occurs by way of two processes, the new study shows. First, a molecule derived from vitamin A called retinoic acid is broken down to limit the creation of blue cones. Second, thyroid hormones encourage 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,” Johnston said. “That’s very important because if you have those blue cones in there, you don’t see as well.”  

The findings offer a different perspective to the prevailing theory that blue cones migrate to other parts of the retina during development. Instead, the data suggest that these cells convert to achieve optimal cone distribution in the foveola. 

“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.” 

The insights could pave the way for new therapies for vision loss. Johnston and his team are working to refine their organoid models to better replicate human retina function. These advancements could lead to improved photoreceptors and potential cell-based treatments for eye diseases such as macular degeneration, which have no cure, said author Katarzyna Hussey, a former doctoral student who graduated from Johnston’s lab.  

“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,” said Hussey, who is now a molecular and cell biologist at cell therapy company CiRC Biosciences in Chicago. “These are very long-term experiments, and of course we’d need to do optimizations for safety and efficacy studies prior to moving into the clinic. But it’s a viable journey.” 

 

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