Johns Hopkins University researchers report that a vitamin A-derived molecule and thyroid hormones help shape the fetal development of the foveola—the small central retinal region responsible for the sharpest human vision—by guiding how cone cells are specified and later change identity.
The research, published in the Proceedings of the National Academy of Sciences, used lab-grown retinal tissue known as organoids—small clusters grown from fetal cells that mimic parts of the developing human retina—to examine how cone photoreceptors form and organize in the foveola.
According to the researchers, blue-light–sensing cone cells (S-cones) appear transiently in the developing foveola during fetal weeks 10 through 12. By about week 14, those cells no longer appear as blue cones in the foveola, with evidence indicating they have converted into red- and green-light–sensing cones (L- and M-cones), which dominate the mature foveola.
The team reported a two-step signaling sequence behind that shift. First, retinoic acid—a molecule derived from vitamin A—is broken down, which reduces the formation of additional blue cones. Then thyroid hormone signaling promotes the remaining blue cones to convert into red and green cones.
"We can’t really rule that out yet, but our data supports a different model," Robert J. Johnston Jr., an associate professor of biology at Johns Hopkins who led the research, said of the longstanding idea that blue cones migrate away from the center. "These cells actually convert over time, which is really surprising."
The foveola is a tiny central region of the retina that is responsible for the sharpest vision and, despite its small size, accounts for about half of human visual perception, the researchers said.
Johnston said the findings could help researchers build lab-grown retinal tissue that more closely resembles the human retina and could eventually support efforts to develop cell replacement approaches for vision loss from age-related eye diseases. The team and other scientists caution that any clinical applications would require further work, including optimization as well as safety and efficacy testing before use in patients.
