Some 250 million years ago, when dinosaurs roamed the Earth and early mammals were little more than tiny, fuzzy creatures that scurried around attempting to evade notice, our ancestors evolved a nifty trick.
Mammals may no longer have to hide from the dinosaurs, but we bear the indelible marks of our scrappy, nocturnal past. Unlike every other vertebrate on land and sea, we still have rod-dominated eyes — human retinas, for example, are 95 percent rods, even though we're no longer active at night.
"How did that happen? What is the mechanism that made mammals become so different?" asked Anand Swaroop, chief of the Neurobiology Neurodegeneration and Repair Laboratory at the National Eye Institute.
He provides some answers to those questions in a study published in the journal Developmental Cell Monday. The findings are interesting from an evolutionary standpoint, he said, but they're also the keys to a medical mystery. If Swaroop and his colleagues can understand how our eyes evolved, perhaps they can fix some of the problems that evolved with them.
For most of history, vertebrate retinas were made up of mostly cone cells, which respond to very particular wavelengths of light to help animals detect color. Creatures from older vertebrate lineages, like reptiles, amphibians, fish and birds, still have this kind of eye.
But when nearly mammals moved into a nocturnal niche during the Triassic, natural selection favored individuals that could see in the dark.
They did this, Swaroop says, by turning some of their cones into rods, which are so sensitive they can detect a single photon of light. Swaroop and his team examined developing photoreceptor cells in embryonic mice to see which genes were active. They found that the precursors to rods were expressing some of the genes normally seen in short wavelength cones (which detect ultraviolet and blue light). Later on in development, a protein called NRL would swoop in and halt that expression, ensuring that the cells became rods instead.
In creatures like zebrafish, on the other hand, rods develop completely differently — suggesting that the NRL-regulated process came about after mammals split off from the rest of our vertebrate relatives.
"Rods must have evolved twice," Swaroop said -- once to create the few rods we see in fish, birds, reptiles and amphibians, and a second time from short wavelength cones in mammals.
That a cell type can be changed so fundamentally with a single protein is exciting to Swaroop, who specializes in studying degenerative eye diseases. It suggests that the cells can also be changed back.
That's significant because, unlike humans and other mammals, creatures with cone-dominated retinas seem to be able to regenerate lost photoreceptors when their eyes are damaged.
"It is possible that the acquisition of rod dominance led to loss of that regenerative capability," Swaroop said. "One can imagine that maybe we could change some of the rods to cones and find some ways to have that regenerative potential in our retina again."
Already, Swaroop and his colleagues have used the NRL protein to maintain some cone cells in mice that are going blind. Turning that into a therapy for humans is a very, very distant prospect, Swaroop acknowledged, but it helps motivate his work.
"It shows that it is possible to do these things," he said. "Nature has been very clever in changing things around for whatever is needed."
If we keep studying nature, he added, perhaps we can adopt some of that cleverness.