“We think that in this early deuterostome, the median eye contained both ciliary and rhabdomeric cells,” Kafetzis explains. As a result, both cellular lineages were incorporated into a single, ancient, cyclopean eye, which later evolved into the vertebrate eyes.

The vertebrate third eye

A trace of this transformation may still survive in the pineal complex at the base of the brain—often referred to as a vertebrate “third eye.” Scientists have long recognized striking similarities between the retina and the pineal organ, leading many to suspect that the two evolved from a single ancestral structure, with the pineal representing a more rudimentary version.

Kafetzis and his colleagues see it differently.

Many researchers suspect that one class of neurons—the bipolar cells—is unique to the retina and represents a key evolutionary innovation of the vertebrate eye. Bipolar cells connect rods and cones to ganglion cells (hence the name “bipolar”). “We think that these bipolar-like cells already exist in the pineal,” says Kafetzis. “It’s just that they don’t look like the typical bipolar—they don’t have a cell before and a cell after.”

For this reason, Kafetzis and his colleagues argue that bipolar neurons are not a de novo evolutionary invention but instead have a chimeric origin, blending features of both rhabdomeric and ciliary cells and bridging the two photoreceptor lineages.

Though grounded in existing ideas and data, the new proposal offers a potentially far-reaching synthesis. Several aspects still require firmer evidence. The idea that the ancestral chordate adopted a burrowing lifestyle remains debated, and the claim that early bilaterians already possessed paired lateral eyes is still speculative.

The authors acknowledge that their model now needs testing. In the paper, they lay out several ways to do so—from molecular comparisons of pineal and retinal cells to developmental studies and broader sampling of eye development across other deuterostome species.

“We want to put forward some literature-based and inspired hypotheses that are testable, and now we can go out and test them,” concludes Kafetzis.

Cell, 2026.  DOI: 10.1016/j.cell.2025.12.056

Federica Sgorbissa is a science journalist; she writes about neuroscience and cognitive science for Italian and international outlets.