An international research team including neuroscientists Henrik Mouritsen and Karin Dedek has made a surprising discovery: Bird retinas – among the most energy-demanding tissues in the animal kingdom – operate permanently without oxygen.
In a study published in Nature, an international research team including Prof. Dr Henrik Mouritsen and Prof. Dr Karin Dedek at the Institute of Biology and Environmental Sciences reveals how birds have solved a biological paradox. The researchers show that the inner layers of the bird retina function under chronic oxygen deprivation and rely on anaerobic energy production. At the same time, the study overturns a centuries-old assumption about the function of a mysterious structure in the bird eye.
A research team led by Professors Christian Damsgaard and Jens Randel Nyengaard at Aarhus University in Denmark asked how the retina of birds is supplied with energy despite the absence of blood vessels. “The retina is a tissue made up of nerve cells that consume a lot of energy. It is, so to speak, a highly specialised extension of the brain,” explains Mouritsen. The Oldenburg neuroscientist was involved in developing the idea for the study.
In most animals, neural tissues are supplied with oxygen through dense networks of tiny blood vessels. This is considered essential, as neurons have exceptionally high energy demands. The retina, a highly specialized extension of the brain, is no exception.
Birds, however, represent a striking exception. Their retinas are avascular, meaning they lack blood vessels within the retinal tissue itself. While this improves visual acuity by reducing light scattering, it raises a fundamental physiological question: how can such an energy-hungry neural tissue function without oxygen?
“Our starting point was simple,” says first author Christian Damsgaard. “According to everything we know about physiology, this tissue should not be able to function.”
No oxygen where it was assumed to be
For centuries, the prevailing explanation was that oxygen was supplied to the retina by the pecten oculi, a comb-like, highly vascularized structure protruding into the vitreous body of the bird eye. Although known since the 17th century, its function had never been directly tested.
Direct measurements of oxygen levels in the bird retina are technically extremely challenging. In 2020, the researchers succeeded in performing such measurements through collaboration with veterinary anesthesia specialists.
The results were unexpected: the pecten oculi does not deliver oxygen to the retina. Instead, measurements showed that roughly half of the retinal tissue exists in a state of permanent oxygen deprivation.
Each answer raised new questions
If the retina receives no oxygen, how does it produce enough energy to function?
To address this, the researchers used spatial transcriptomics to map the activity of thousands of genes directly within the retinal tissue. The data revealed a clear pattern: genes involved in anaerobic glycolysis- the breakdown of sugar without oxygen – were highly active in the oxygen-deprived inner layers of the retina.
This immediately raised another puzzle. Anaerobic glycolysis produces roughly fifteen times less energy per sugar molecule than oxygen-based metabolism, despite the retina’s extremely high energy demand.
A new role for an old structure
Further imaging studies using radiolabelled glucose showed that the bird retina takes up sugar at much higher rates than the rest of the brain.
Returning to the pecten oculi, the researchers identified high expression of glucose and lactate transporters in the structure. Rather than supplying oxygen, the pecten functions as a metabolic gateway – delivering glucose into the retina and removing lactate, a waste product of anaerobic metabolism, back into the bloodstream.
Oldenburg neuroscientists Karin Dedek and Henrik Mouritsen demonstrated that certain supporting cells in the retina, known as Müller cells, ensure glucose reaches nerve cells while transporting lactate away. Using antibodies, the two researchers proved that these cells contain the necessary enzymes for transporting lactate and glucose. They also developed a model showing how lactate and glucose are exchanged between the eye chamber, the vitreous body, and the Müller cells, enabling highly effective anaerobic glycolysis in the nerve cells of the retina.
“The pecten is not an oxygen supplier,” says senior author Jens Randel Nyengaard. “It is a transport system for fuel in and waste out.”
Evolutionary and medical perspectives
Avoiding oxygen and blood vessels in the retina likely provides an optical advantage by improving visual sharpness. Evolutionary evidence suggests that this trait arose in the dinosaur lineage that later gave rise to modern birds.
Although the study is fundamental research, the authors note that the findings may inform future thinking about diseases involving oxygen deprivation.
“In conditions like stroke, human tissues suffer because oxygen delivery is reduced and metabolic waste accumulates,” Nyengaard says. “In the bird retina, we see a system that copes with oxygen deprivation in a very different way.”
This text is based on a press release from the University of Aarhus.
