The retina is one of the most energy-intensive tissues in the body. With its many nerve cells lying close together, our visual organ needs large amounts of oxygen and is therefore heavily supplied with blood. In birds, however, there are no blood vessels in the retina. For centuries, science assumed that the visual cells got oxygen in other ways. However, a study now shows that the inner areas of the bird retina actually function completely without oxygen and instead metabolize glucose anaerobically. Although this process is significantly less efficient, it may have helped birds develop exceptional visual acuity over the course of evolution.
Nerve cells have a particularly high need for oxygen. Even just a few minutes without the vital energy source can cause irreversible damage. For example, if a person’s brain is not sufficiently supplied with blood for a short time after a stroke, the affected neurons die and cannot be restored. The nerve cells are particularly densely packed in the retina. In most animals, this is crossed by a dense network of blood vessels that ensure the energy supply.
Mysterious structure in focus
Birds are an exception: “In birds, the retina lacks the internal blood vessel system,” explains a team led by Christian Damsgaard from Aarhus University in Denmark. “This raises the question of how such a metabolically intensive nerve tissue can function without blood supply.” For centuries, the prevailing explanation has been that the retina receives oxygen even without blood vessels, through a structure unique to birds called the pecten oculi. This is a comb-like, highly vascular organ that protrudes into the vitreous body of the bird’s eye. This structure has been known since the 17th century, but its exact function has remained speculative.
Damsgaard and his colleagues have now measured the oxygen content in the retinas of pigeons, chickens and zebra finches and discovered that there is a permanent lack of oxygen in the inner layers of the retina. About half of the retinal tissue has to survive without oxygen. But where do the nerve cells get the energy to maintain their function? To answer this question, the researchers examined gene expression in different parts of the bird retina. “We examined not just one or two genes, but 5,000 to 10,000 genes at once, each assigned to a specific location,” says Damsgaard. “That gave us a kind of molecular GPS.”
Anaerobic sugar degradation
The data showed: Genes that are involved in so-called anaerobic glycolysis, i.e. the breakdown of sugar without oxygen, were active in the oxygen-poor inner layers of the retina. However, this process delivers fifteen times less energy per glucose molecule than if the sugar was simply burned using oxygen. “This discrepancy raised another question,” says Damsgaard’s colleague Jens Nyengaard: “How can one of the most energy-hungry tissues in the body survive with such an inefficient process?”
The answer was provided by further imaging studies in which the researchers radioactively labeled sugar molecules in order to follow their route to the nerve cells. According to this, the retina of birds absorbs much more sugar than the rest of the brain. This is where the pecten oculi comes into play: It transports glucose to the retina and removes the waste lactate, which is produced during anaerobic metabolism. The structure, which has been enigmatic for centuries, actually forms an interface between the non-perfused retina and the bloodstream – only not for oxygen, as previously assumed, but for glucose. “The pecten is not a supplier of oxygen. It is a transport system that moves fuel in and waste materials out,” says Nyengaard.
Learning from evolution for medicine
Evolutionarily, this system probably had the advantage for birds in that it allowed them to see further and more clearly. Because when blood vessels pass through the retina, they can scatter the incident light and thereby reduce the resolution of the perceived image. The tolerance of the visual cells to a lack of oxygen is also important when birds travel to high altitudes where the air is thin. If their energy-intensive eyes were dependent on oxygen, high altitude flights would result in cell death and thus loss of vision.
Medicine could possibly also learn something from the bird’s eye. “In diseases such as strokes, human tissues suffer from reduced oxygen supply and accumulation of metabolic waste,” says Nyengaard. “In the bird retina we see a system that deals with a lack of oxygen in a completely different way. We hope that understanding this evolutionary solution can provide new ideas about why tissues fail in the absence of oxygen during illness and how such diseases can be treated.”
Source: Christian Damsgaard (Aarhus University, Denmark) et al., Nature, doi: 10.1038/s41586-025-09978-w