Humans develop sharp\u00a0vision 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.\u00a0<\/p>\n
The findings\u00a0could upend\u00a0decades of conventional\u00a0understanding\u00a0of how the\u00a0eye\u00a0grows\u00a0light-sensing cells\u00a0and could\u00a0inform\u00a0new research into treatments for macular degeneration, glaucoma, and other age-related vision disorders.\u00a0<\/p>\n
Details of the study, which used lab-grown retinal tissue, are published today in\u00a0Proceedings of the National Academy of Sciences.<\/p>\n
“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,”\u00a0said\u00a0Robert J. Johnston Jr., an associate professor of biology at Johns Hopkins\u00a0who 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.”\u00a0<\/p>\n
In recent years, the team pioneered a new method to study\u00a0eye\u00a0development\u00a0using\u00a0organoids,\u00a0small tissue\u00a0clusters\u00a0grown from fetal cells.\u00a0By\u00a0monitoring\u00a0these lab-grown retinas over several months, the researchers discovered the cellular mechanisms that\u00a0shape the foveola-a central retinal region responsible for sharp\u00a0vision.\u00a0<\/p>\n
Their research focused on\u00a0light-sensitive cells that enable\u00a0daytime\u00a0vision.\u00a0These cells develop into blue, green, or red cone\u00a0cells\u00a0that\u00a0have\u00a0sensitivity to\u00a0different types\u00a0of light. Although the foveola comprises only a small fraction of the retina, it accounts for about 50% of human visual perception.\u00a0The foveola\u00a0contains\u00a0red and green cones but\u00a0not\u00a0blue cones, which are distributed more broadly across the rest of the retina.\u00a0<\/p>\n
Humans are unique in having these three types of cones for color vision, allowing\u00a0people\u00a0to see a wide spectrum of colors that\u00a0are\u00a0relatively rare\u00a0in other animals. How eyes grow with this distribution of cells has puzzled scientists\u00a0for decades. Mice, fish, and other organisms commonly used for biological research do not have\u00a0this patterning of\u00a0cells, which makes the photoreceptor cells difficult to study, Johnston said.\u00a0<\/p>\n
The Johns Hopkins team\u00a0concluded\u00a0the distribution of cones in the foveola results from a coordinated process of cell fate specification and conversion during early development. Initially, a sparse\u00a0number\u00a0of blue cones are present in the foveola\u00a0at weeks 10 through 12. But, by week 14, they transform into red and green\u00a0cones. The\u00a0patterning\u00a0occurs by way of two processes,\u00a0the\u00a0new 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\u00a0encourage\u00a0blue cones to convert into red and green cones.\u00a0<\/p>\n
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.”\u00a0<\/p>\n
Robert J. Johnston Jr., associate professor of biology, Johns Hopkins University<\/p>\n
The findings\u00a0offer\u00a0a different perspective\u00a0to the\u00a0prevailing theory that blue cones migrate to other parts of the retina during development. Instead, the data suggest that these cells convert to achieve\u00a0optimal\u00a0cone distribution in the foveola.\u00a0<\/p>\n
“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\u00a0can’t\u00a0really rule that out yet, but our data supports a different model. These cells\u00a0actually convert\u00a0over time, which is\u00a0really surprising.”\u00a0<\/p>\n
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\u00a0such as macular degeneration,\u00a0which have no cure, said\u00a0author Katarzyna Hussey, a former doctoral student\u00a0who graduated from\u00a0Johnston’s lab.\u00a0<\/p>\n
“The goal\u00a0with\u00a0using this organoid tech\u00a0is\u00a0to\u00a0eventually 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,”\u00a0said\u00a0Hussey, who is now a molecular and cell biologist at cell therapy company\u00a0CiRC\u00a0Biosciences in Chicago. “These are very long-term experiments, and of course\u00a0we’d\u00a0need to do optimizations for safety and efficacy<\/a> studies prior to moving into the clinic. But\u00a0it’s\u00a0a viable\u00a0journey.”\u00a0<\/p>\n Source:<\/p>\n Journal reference:<\/p>\n