Lab grown eyes crack why we see millions of colors that cats, dogs don’t

Humans have the exceptional ability to sense colors, unlike any other organism on the Earth. Scientists have been attempting to understand the diverse underlying processes that contribute to our unique ability to see a wide range of colors. Lab grown retinas have now shown how humans perceive hundreds of hues — a capability that dogs, cats, and other animals do not share.

Researchers at Johns Hopkins University analyzed retinal organoids in depth to learn more about the processes that drive the formation of color sensing cells. “These retinal organoids allowed us for the first time to study this very human specific trait. It’s a huge question about what makes us human, what makes us different,” said author Robert Johnston, an associate professor of biology, in the release.

Contrary to previous beliefs that thyroid hormones controlled the process of color sensing cell development, the research team identified retinoic acid as a key player. Variation between the ratio of green and red cone cells In this study, the scientists made minor changes to the organoids' cellular features.

The results showcased that the specialization of cone cells in detecting either red or green light is determined by the presence of retinoic acid. Cone cells are specialized photoreceptor cells found in the retina of the human eye. These cells are critical to the sense of color. Cone cells are classified into three types, each of which is sensitive to distinct wavelengths of light and detects specific colors: red, green, and blue.

The combined signals from these three types of cones enable humans to see a wide spectrum of colors. What surprised researchers the most was the varying ratios of green and red cone proportions in humans. The study revealed that the presence of high levels of retinoic acid in the early stages of organoid development was associated with a larger proportion of green cones.

In contrast, smaller doses of the acid changed the genetic instructions in the retina, resulting in the formation of red cones later in development. “There still might be some randomness to it, but our big finding is that you make retinoic acid early in development. This timing really matters for learning and understanding how these cone cells are made,” added Johnston.

Additionally, they mapped the ratio variations in the retinas of 700 adults and observed that it did not have an impact on an individual's vision. Still gaps in this understanding The study also notes that, despite the genes of green and red cone cells being 96% similar, they differ in one aspect, specifically the protein known as opsin.

This protein aids in the detection of light and transmits information to the brain about the colors observed. The researchers also searched for tiny genetic alterations in the retina organoids, which allowed them to precisely watch how the ratio changed over 200 days. “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.

That has implications for figuring out exactly how retinoic acid is acting on genes,” said Sarah Hadyniak, one of the authors, in the The team highlights that there are still gaps in their understanding of the observed differences in the ratio of green and red cones in the retina. Nonetheless, this novel technique opens up new possibilities for understanding color blindness, age related visual loss, and disorders involving photoreceptor cells.

The details were reported in the journal Trichromacy is unique to primates among placental mammals, enabled by blue (short/S), green (medium/M), and red (long/L) cones. In humans, great apes, and Old World monkeys, cones make a poorly understood choice between M and L cone subtype fates. To determine mechanisms specifying M and L cones, we developed an approach to visualize expression of the highly similar and mRNAs.

was observed before expression during early human eye development, suggesting that M cones are generated before L cones. In adult human tissue, the early developing central retina contained a mix of M and L cones compared to the late developing peripheral region, which contained a high proportion of L cones.

Retinoic acid (RA) synthesizing enzymes are highly expressed early in retinal development. High RA signaling early was sufficient to promote M cone fate and suppress L cone fate in retinal organoids. Across a human population sample, natural variation in the ratios of M and L cone subtypes was associated with a noncoding polymorphism in the gene, a mediator of RA signaling.

Our data suggest that RA promotes M cone fate early in development to generate the pattern of M and L cones across the human retina..