These cave fish lost their eyes, again and again, and they could hold the key to fighting obesity.

Mexican tetras are a very peculiar species of fish . They are found in many rivers and lakes in Mexico and South Texas, where they look perfectly normal. But, unlike most other fish, tetras also live in caves. And there, in the absence of light, they look radically different: they are very pale and, surprisingly, lack eyes.

Time and again, every time a population was dragged into a cave and survived long enough for natural selection to do its work, the eyes disappeared. “But it’s not like cave fish have lost everything,” says geneticist Jaya Krishnan of the Oklahoma Medical Research Foundation. “There have also been many improvements.”

Although the disappearance of their eyes continues to fascinate biologists, in recent years attention has shifted to other intriguing aspects of cave fish biology. It is increasingly clear that they have not only lost their sight, but have also acquired many adaptations that help them thrive in the cave environment, including some that may hold clues for treating obesity and diabetes in humans.

Getting rid of expensive eyes

The reason for the loss of eyes has long been debated. Some biologists used to argue that they simply atrophied over generations because cave-dwelling animals with defective eyes experienced no disadvantage. But another explanation is now considered more likely, according to evolutionary physiologist Nicolas Rohner of the University of Münster in Germany: “Eyes are very expensive in terms of resources and energy. Most people now agree that there must be some advantage to losing them, if they are not needed.”

Scientists have observed that mutations in different genes involved in eye formation have caused their loss . In other words, Krishnan says, “different cavefish populations have lost their eyes in different ways.”

Meanwhile, the fish's other senses tend to have become more enhanced. Studies have found that cave-dwelling fish can detect lower levels of amino acids than surface-dwelling fish. They also have more taste buds and a higher density of sensory cells along their bodies that allow them to sense water pressure and flow.

The brain regions that process other senses have also expanded, says developmental biologist Misty Riddle of the University of Nevada, Reno, who co-authored a 2023 paper on the Mexican tetra research . “I think what’s happened is that you have to sort of kill the eye program to expand the other areas.”

What happens is that the processes that support eye formation are eliminated. Like non-cave-dwelling members of the species, all cavefish embryos begin to develop eyes. But after a few hours, the developing eye cells begin to die , until the entire structure disappears. Riddle believes this apparent inefficiency may be inevitable. “Early brain and eye development are completely intertwined—they happen at the same time,” he says. That means the least disruptive way to develop eyelessness may be to start forming them and then get rid of them.

In what Krishnan and Rohner have called “one of the most striking experiments ever conducted in the field of vertebrate evolution,” a study published in 2000 showed that the fate of a cavefish’s eye is greatly influenced by its lens . The scientists demonstrated this by transplanting the lens of a surface-dwelling fish embryo into a cavefish embryo, and vice versa. In doing so, the cavefish’s eye developed a retina, rods, and other important eye parts, while the surface-dwelling fish’s eye remained small and underdeveloped.

Hunger and binge eating

It's easy to see why cave fish would be at a disadvantage if they had to maintain expensive tissues they don't use. Since relatively little lives or grows in their caves, the fish likely survive on a meager diet, composed primarily of bat droppings and organic debris that arrives with the rainy season. Researchers who maintain cave fish in laboratories have discovered that, genetically, these creatures are exquisitely adapted to absorb and store nutrients. "They're constantly hungry and eat whatever they can," Krishnan says.

Interestingly, fish have at least two mutations associated with diabetes and obesity in humans. However, in cave fish, these mutations may underlie some very useful traits for a fish that occasionally has plenty of food, but often has nothing. When scientists compare cave fish and surface fish kept in the lab under the same conditions, the cave fish fed regular amounts of standard fish food “put on weight.” “They have high blood sugar levels,” says Rohner. “But, interestingly, they don’t develop obvious signs of disease.”

Fats can be toxic to tissues, Rohner explains, so they are stored in fat cells. “But when these cells get too large, they can burst, which is why we often see chronic inflammation in humans and other animals that have stored a lot of fat in their tissues.” However, a 2020 study by Rohner, Krishnan, and colleagues revealed that even well-fed cave fish showed fewer signs of inflammation in their fat tissues than surface fish.

Even in the sparse conditions of caves, wild cave fish can sometimes become very fat, says Riddle. This is probably because, when food arrives in the cave, the fish eat as much as they can, as there may be nothing else around for a long time. Interestingly, says Riddle, their fat is often bright yellow, due to high levels of carotenoids, the substance found in carrots that our grandmothers told us was good for our eyes.

“The first thing we came up with, of course, was that they accumulate them because they don’t have eyes,” says Riddle. In this species, these ideas can be put to the test: scientists can cross surface fish (with eyes) and cave fish (without eyes) and observe what their offspring look like. Once this is done, says Riddle, the researchers see no relationship between the presence or size of eyes and carotenoid accumulation. Some eyeless cave fish had practically white fat, indicating lower carotenoid levels.

Instead, Riddle believes these carotenoids may be another adaptation to suppress inflammation, which could be important in the wild, since cave fish are likely to overeat whenever food arrives.

Studies by Krishnan, Rohner, and their colleagues published in 2020 and 2022 have uncovered other adaptations that appear to help reduce inflammation. The cavefish’s cells produce lower levels of certain molecules called cytokines that promote inflammation , as well as lower levels of reactive oxygen species , tissue-damaging byproducts of the body’s metabolism that are often elevated in people with obesity or diabetes.

Krishnan is investigating this further, hoping to understand how well-fed cave fish stay healthy. Rohner, for his part, is increasingly interested in how cave fish survive not only overfeeding, but also long periods of starvation.

No waste

At a more fundamental level, researchers still hope to discover why the Mexican tetra evolved toward cave-dwelling behavior, while other Mexican river fish that also tend to end up in caves did not. Worldwide, there are more than 200 species of cave-adapted fish, but those that also have surface populations are quite rare. “You might assume there’s something in the genetic makeup of tetras that makes it easier for them to adapt,” Riddle says.

Although cave fish are now well-established laboratory animals used in research and are easily acquired for that purpose, it's important to preserve them in their natural habitat to safeguard the lessons they can still teach us. "There are hundreds of millions of fish at the surface," says Rohner, but cave fish populations are smaller and vulnerable to pressures such as pollution and water extraction from caves during droughts.

One of Riddle's students, David Pérez Guerra, now serves on a committee to support the conservation of cave fish. And the researchers themselves are also becoming more careful. "The fish tissues collected during our last lab field trip benefited nine different labs," says Riddle. "We didn't waste anything."

Article translated by Debbie Ponchner .

This article originally appeared on Knowable en español , a nonprofit publication dedicated to making scientific knowledge accessible to everyone.