The mouse eye captures images via rods and cones in its retina. But behind that
gaze lies a third set of light-sensitive cells that contribute to behavior, not to vision.

iStockphoto

There was no way the blind mice could see, yet somehow, they could. The year was 1923, and a Harvard grad student named Clyde Keeler had set out to compare eyes from different animals, starting with mice that he bred in his dorm room. Keeler cut open one mouse’s eye and put it under a microscope. Immediately he realized something was wrong. Missing from the eye was the layer of rods and cones, the photoreceptors that catch light. Turning back to his colony, Keeler realized that half of his animals were blind. Somehow a mutation had arisen, wiping out their rods and cones.

The mutation had blinded those mice with surgical precision, yet for reasons lost to history, Keeler got the strange idea to shine a light in their eyes anyway. Based on everything that scientists knew about mammalian eyes, nothing should have happened. After all, the mice had no way to capture light and relay it to the retinal ganglion cells, the neurons that normally pass visual signals on to the brain. And yet something did happen: The mouse pupils shrank.

Keeler struggled to find an explanation. “We may suppose that a rodless mouse will not see in the ordinary sense,” he wrote in one journal article. But for pupils to shrink, such mice had to have some kind of cell besides rods and cones—one that scientists knew nothing about—that could also capture light and send a signal to the brain.


Most vision experts scoffed at the notion that the eyes contained hidden sensory cells and ignored Keeler’s findings. It took nearly eight decades for scientists to investigate his claim and prove him right: The eye really does contain a third type of photoreceptor cells that sense light intensity without detecting images.

These sightless cells seem to perform a variety of important functions. They set our body clock and regulate our sleep. They may explain why bright light can trigger migraines. They may even reveal why depression is so commonly associated with winter’s darker days.

Some of the first validation of Keeler’s research came in the 1990s from University of Oxford neuroscientist Russell Foster, who studied the daily cycle of our bodies—the so-called circadian rhythms that define the pattern of vital signs in a 24-hour day. We become sleepy and then alert; our body temperature cools and then warms; hormones are released, then subside. The changing level of light each day keeps these rhythms synchronized with Earth’s rotation. If people live in windowless rooms for days on end, experiments have shown, their circadian rhythms gradually drift out of sync, so that they might end up sleeping in the daytime and staying awake all night.

Yet no one knew exactly how light acts as a reset button. To search for a mechanism, Foster ran a new experiment. He essentially re-created Keeler’s blind mice by shutting down genes essential for the development of rods and cones while still exposing his subjects to cycles of light and dark. Foster also set up the same experiment using mice with normal eyes. If the rods and cones acted as the reset button, then the circadian rhythms of the sighted mice should hold to the classic pattern while circadian rhythms of the blind mice drift away. But that’s not what 
happened. In 1999 Foster reported that the blind mice behaved the same as regular mice. Only when Foster surgically removed their entire eyes did the blind mice drift out of sync. Keeler’s sightless cells must have been at work.

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