Almost every living thing has eyes (save for a few) but they don’t use them the same way. Humans, for example, see in technicolor and well-lit spaces, while dogs predominantly see yellow and blue only. Fish need to see underwater, and owls can’t see color very well but have excellent night vision.
With all of the different ways animals use their eyes, one might assume cells types in eyes between species vary drastically. But a new study by researchers at the University of California, Berkeley shows the opposite. In fact, the researchers’ data shows that the retina of vertebrate species, such as mice and humans, are remarkably conserved since the origin of jawed vertebrates more than 400 million years ago.
“What we are seeing is that something thought to be unique to primates is clearly not unique. It’s a remodeled version of a cell type that is probably very ancient,” said study author Karthik Shekhar, a UC Berkeley assistant professor of chemical and biomolecular engineering. “The early vertebrate retina was probably extremely sophisticated, but the parts list has been used, expanded, repurposed or refurbished in all the species that have descended since then.”
For the study, published in Nature, Shekhar and colleagues gathered eyes from 17 species: human, two monkeys (macaque and marmoset), four rodents (three species of mice and one ground squirrel), three ungulates (cow, sheep and pig), tree shrew, opossum, ferret, chicken, lizard, zebrafish and lamprey.
Through transcriptomic experiments and computational analysis, the team identified many new cell types in each of the species. They then mapped this variety to a smaller set of “orthotypes”—cell types that have likely descended from the same ancestral cell type in early vertebrates.
For bipolar cells, which are a class of neurons that lie between the photoreceptors and retinal ganglion cells, the team found 14 distinct orthotypes. Most extant species contain 13 to 16 bipolar types, suggesting that these types have evolved little.
In contrast, the researchers found 21 orthotypes of retinal ganglion cells, which exhibit greater variation among species. Studies thus far have identified more than 40 distinct types in mice and about 20 different types in humans.
Specifically, the scientists were surprised to find that the midget retinal ganglion cell, which is responsible for humans’ ability to see fine detail, is not unique to primates as it was previously thought to be. The team discovered evolutionary counterparts of midget cells in all other mammals, though these counterparts occurred in much smaller proportions.
The authors say the pronounced evolutionary divergence among types of retinal ganglion cells, as compared with other retinal classes, suggests that natural selection acts more strongly on diversifying neuron types that transmit information from the retina to the rest of the brain. Lastly, the study results showed numerous transcription factors to be highly conserved, suggesting that the molecular steps leading to the development of the retina might be evolutionarily conserved, as well.
Based on the results of this new study, Shekhar is refocusing his glaucoma research on the analogs of midget cells. While mice are the favored animal model for studying glaucoma, they have very few of the midget retinal ganglion cell counterparts. These cell types make up only 2% to 4% of all ganglion cells in mice, whereas 90% of retinal ganglion cells are midget cells in humans.
“This work is clinically important because, ultimately, the midget cells are probably what we should care about the most in human glaucoma,” Shekhar said. “Knowing their counterparts in the mouse will hopefully help us design and interpret these glaucoma mouse models a little better.”