Vitamin A Metabolite Explains Why Humans See Colors Dogs Can’t

Have you ever wondered why dogs and cats can only see a limited color spectrum, while humans are able to envision a spectrum that is millions of colors-wide? Researchers from John Hopkins University set out to understand this phenomenon using lab-grown human retinas in their study published in PLoS Biology.

How do these color-sensing cells develop?

During early embryogenesis, the NR2F2 gene instructs the human retina to produce cone cells that specialize in sensing red or green light.

Only humans with normal vision and closely related primates possess the ability to develop the red sensor. Until recently, this process was thought to be random, though there has been some research to suggest it may also be partially driven by thyroid hormones.

Dr. Robert Johnston, an associate professor of biology at John Hopkins University and his team have discovered that an offshoot of vitamin A – retinoic acid – is the main orchestrator of this mechanism.

Growing human retina cells in a petri dish

Johnston and colleagues grew retinal organoids with different cellular properties to determine why certain cone cells developed to sense different colors. They discovered that high levels of retinoic acid during early development of the organoids were associated with a higher number of green sensing cones, whereas lower levels correlated with red cones generated later in development.

The team also tracked cone ratio changes over 200 days in the retinas of 700 adults, which appeared to vary greatly across individuals. “Seeing how the green and red cone proportions changed in humans was one of the most surprising findings of the new research,” said author Dr. Sarah Hadyniak, who conducted the research as a doctoral student in Johnston’s lab.

It is still not fully understood how the ratio of these green and red cones can vary so greatly without affecting someone’s vision. “If these types of cells determined the length of a human arm, the different ratios would produce ‘amazingly different’ arm lengths,” Johnston said.

Implications for diseases related to photoreceptor cells

“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 Hadyniak. “That has implications for figuring out exactly how retinoic acid is acting on genes.”

The research hopes to improve our understanding of color blindness, age-related vision loss and other diseases like macular degeneration going forward.

“The future hope is to help people with these vision problems. It's going to be a little while before that happens, but just knowing that we can make these different cell types is very, very promising,” Johnston said.

Reference: Hadyniak SE, Eldred KC, Brenerman B, et al. Retinoic acid signaling regulates spatiotemporal specification of human green and red cones. PLOS Biology. 2024. doi: 10.1371/journal.pbio.3002464

This article is a rework of a press release issued by John Hopkins University. Material has been edited for length and content.