A new study on chicken embryos may help researchers understand how humans developed their sensitive daylight vision.
Humans are one of just a few species that experience acute color vision in bright daylight, along with apes and some fish, birds, and reptiles. This sensitive daytime vision is a result of the fovea, a small depression near the center of the human retina where visual acuity is the highest. While scientists understand how the fovea works, it is unclear exactly how it is formed during embryonic development.
“I think it’s important to understand how you build this specialized area in the retina,” said Susana da Silva, a postdoctoral fellow at Harvard Medical School. “[It’s] responsible for any major activity you do during the day, such as reading, driving, recognizing faces and using the phone.”
Researchers may soon have an answer to the question of the fovea’s origin, and it could all be thanks to chickens. Like humans, chickens also have a high-acuity region in their eyes. The human retina contains cone cells, which respond to bright light and color, and rod cells, which are responsible for vision in dim light. Both the human fovea and the high-acuity area in a chicken eye contain virtually no rods and are populated almost exclusively by cones. They also share similar structural characteristics.
These similarities encouraged Connie Cepko, a Professor of Genetics at Harvard Medical School, and da Silva to begin studying chicken eyes to better understand the fovea, and the researchers now know how the high-acuity area in a chicken eye is formed. According to their study published in the journal Developmental Cell, the secret lies in the suppression of retinoic acid, a derivative of vitamin A that serves a vital role in the development of many animal embryos. Retinoic acid is produced in the retina by enzymes known as Raldhs. However, when Cepko and da Silva observed the formation of cone cells in the eyes of chicken embryos, they found that enzymes called Cyp26a1 and Cyp26c1 broke down retinoic acid faster than Raldhs could produce it. This decline in retinoic acid allowed a protein known as fibroblast growth factor 8, or Fgf8, to thrive, forming the complex cell patterns found in the high-acuity area of the chicken eye.
“This is the first mechanism we’ve uncovered for how this area forms. We don't know where it will lead, but it’s pretty exciting,” Cepko said. Similar expression patterns for Cyp26a1 and Raldhs in human retinal tissue suggest that a similar process could occur in humans.
Cepko and da Silva's research thus brings scientists one step closer to discovering how the fovea develops in human embryos, which could be key to treating people with impaired vision. The leading cause of vision loss among people aged 50 or older is macular degeneration, an incurable eye disease that affects over 10 million Americans. The disease is caused by the deterioration of the macula, the region of the retina in which the fovea is located. “Macular degeneration is a major problem for the aging population, and we don’t understand why that area is vulnerable,” Cepko explained. By learning how the fovea is developed, researchers may better understand why the macula is prone to deterioration and thus improve treatments for macular degeneration.
Cepko and da Silva’s discovery may also help stem cell researchers who wish to replicate the human eye. “People can grow these incredible little eyes from stem cells, but so far no one’s been able to form a fovea,” Cepko explained. “We’re suggesting that removing retinoic acid at the right time, adding Fgf8 or otherwise manipulating these two molecules may allow them to generate a fovea."