Scientists have used human retinas grown in a petri dish to study how humans can see millions of colors, while dogs can only see a limited range of hues. They found that a molecule derived from vitamin A, called retinoic acid, plays a key role in determining whether a cone cell will sense red or green light.
How dogs see the world differently from humans
Dogs have two types of cone cells in their retina, which are responsible for color vision. They can sense blue-violet and yellow, and combinations of those colors. They cannot see red and green, which are the most common colors for human color blindness. This means that dogs see the world in shades of blue, yellow and gray .
Humans, on the other hand, have three types of cone cells that can sense blue, green, or red light. Only humans with normal vision and closely related primates have the red cone cells, while other mammals lack them. Scientists have long wondered how the human retina decides whether to make green or red cone cells, and whether it is a random or a regulated process.
How retinoic acid controls cone cell development
The researchers, led by Robert Johnston, an associate professor of biology at Johns Hopkins University, published their findings in PLOS Biology on January 11, 2024. They used retinal organoids, which are miniature versions of the human retina that can be grown from stem cells in the laboratory. These organoids allowed them to investigate how retinoic acid, which is derived from vitamin A and is essential for eye development, controls the fate of cone cells.
The new study suggests that retinoic acid is the key factor that controls whether a cone cell will sense green or red light. The researchers found that high levels of retinoic acid in early development of the organoids led to more green cone cells, while low levels of retinoic acid resulted in more red cone cells later in development.
“There still might be some randomness to it, but our big finding is that you make retinoic acid early in development,” Johnston said. “This timing really matters for learning and understanding how these cone cells are made.”
Implications for color vision disorders and eye health
The study also sheds light on how different types of opsin proteins, which detect light and send signals to the brain, determine whether a cone cell will sense green or red light. The genes for green and red opsins are very similar, with only a few differences that affect their sensitivity to wavelengths. The researchers used a novel technique that could detect these subtle genetic differences in the organoids and track how they changed over time.
“Because we can control in organoids the population of green and red cells, we can kind of push the pool to be more green or more red,” said author Sarah Hadyniak, who conducted the research as a doctoral student in Johnston’s lab and is now at Duke University.
The findings could help understand and treat color blindness, which affects about 8% of men and 0.5% of women. Color blindness is caused by mutations in the genes for opsins, which impair the ability to distinguish certain colors. The study could also provide insights into age-related vision loss and other diseases that affect photoreceptor cells.
The researchers plan to further explore how retinoic acid regulates cone cell development and how it interacts with thyroid hormones, which are also involved in eye formation.