The eye is an ecosystem, with its different parts relying on each other to survive.

Your eyes make waste. Without it, you could go blind

One man’s trash is another man’s treasure, even at the level of the cell. That’s where—according to new research—a waste product of the retina fuels part of the eye that powers the rods and cones that help us sense light. Without this waste, that part of the eye “steals” glucose from the retina, leading to the death of retinal cells and likely vision loss. The finding could help explain why eyesight degenerates with age—and in diseases such as macular degeneration and diabetes.

“It’s almost a revolutionary concept” that there is such a tight coupling between the two parts of the eye, says Stephen Tsang, a retina specialist at Columbia University who was not involved in the work.

Rods and cones are very active, and they need a lot of energy to do their jobs. Exactly how they get this energy has long been a mystery. In previous studies, researchers showed that a layer of cells beneath the retina, the retinal pigment epithelium (RPE), ferries glucose from the blood to the retina. But it was unclear why the RPE didn’t keep the glucose for itself.

After a decade of study, biochemist James Hurley at the University of Washington in Seattle and his colleagues have now shown that the retina’s rods and cones burn the glucose, convert leftovers into a fuel called lactate, and then feed that back to the RPE. “There is a growing consensus that no cell exists on its own in complex tissues like the retina,” says Martin Friedlander, an ophthalmologist at The Scripps Research Institute in San Diego, California, who was not involved with the new work.

To precisely map how glucose and lactate move around in the eye, Hurley and colleagues grew human RPE in a lab dish and studied its biochemistry along with that of isolated mouse retinas. They discovered that the RPE’s power plants—the mitochondria—burn lactate to power the RPE. “That allows the glucose to go through without being consumed,” Hurley explains. If they deprive the RPE of lactate, then those cells switch to burning the glucose instead of delivering it to the retina, the team reports this month in eLife. With glucose shut off, the retina cells can die.

“The interplay between the different pathways is really important and [this] work really shows it,” says Deborah Ferrington, a vision science researcher at the University of Minnesota in Minneapolis. Her own work has implicated mitochondrial defects in macular degeneration, indicating a possible connection between vision loss in that disease and glucose starvation. The new work also “gives you the opportunities to find interventions,” she adds.

One of those could be a widely applicable drug or nutritional supplement, says Tsang, who has been involved in developing gene therapy for treating eye diseases. Even though mutations in many genes may result in glucose starvation, “one treatment may treat all the different gene [defects],” he suggests.

The work may also explain a big ophthalmological mystery. Researchers could never understand why cones, which enable us to see in color, die out when rods, which work in dim light, are defective, explains Zsolt Ablonczy, a pharmacologist at the Medical University of South Carolina in Charleston. He says he now realizes that if defective rods fail to make lactate, that may cause the energy-deprived RPE to steal all the glucose, essentially starving both cones and rods. He studies aging effects in the eye, which he thinks may arise in part when there’s an imbalance between lactate or glucose in the RPE. Hurley’s observations are “absolutely fundamental,” he notes.

But Hurley and others caution that researchers must first demonstrate this energy exchange in the eyes of living animals to really know what’s going on. “The observations reported in this study are valuable,” says Friedlander, but it’s unclear how this process works in an eye in a living person, particularly when there are defects. Thus, he adds, “It is still unclear” how the findings could be used to prevent eye disease.