Fugle og fisk gemmer – måske - på nøglen til bedre behandling af blodpropper
Fuglens øjne klarer sig uden ilt, og fiskenes øjne tåler ekstremt meget. Nu undersøger forskere ved Aarhus Universitet, hvordan evolutionens løsninger kan bruges til at hjælpe patienter med kredsløbssygdomme.
If researchers can determine how the cells in a bird’s retina can survive without oxygen, they may have uncovered a mechanism that could help thousands of cardiovascular patients.
At Aarhus University, a research group is therefore investigating how a bird’s nerve tissue functions under conditions similar to those that occur during blood clots in humans.
Leading the project is Christian Damsgaard, an assistant professor at the Section for Zoophysiology, Department of Biology, Aarhus University. He explains that the bird’s retina is particularly interesting because it is unique for tissue to survive without oxygen.
“Normally, cells can only tolerate a lack of oxygen for a few minutes, but a bird’s retina can survive completely without it throughout its entire life. This is fundamentally different from anything we know in other tissues of the animal kingdom,” he says.
Tolerance to oxygen deprivation is relevant in a biomedical context because many cardiovascular diseases involve reduced blood flow.
The patient’s tissue receives less oxygen, and carbon dioxide and lactic acid accumulate, which together cause the tissue to degenerate—something that does not happen in birds.
“Nature has therefore solved a physiological problem in birds that is not present in humans. We are trying to understand the evolution in the hope of finding a solution to something that ultimately makes us ill,” explains Christian Damsgaard.
Makes no physiological sense
The retina of a bird’s eye is transparent so that blood vessels do not block incoming light. This is the result of strong evolutionary pressure on birds’ vision millions of years ago, explains Christian Damsgaard.
Without blood vessels in the eye, the bird can absorb light more efficiently, allowing it to see and hunt better. It can also navigate more effectively and avoid being eaten by predators.
At present, researchers are trying to understand how retinal cells can absorb nutrients without blood vessels and oxygen—and how the cells distribute nutrients among themselves.
“It is a highly metabolic tissue that requires a great deal of energy, but at the same time there is no oxygen present. Physiologically, this makes no sense. On top of that, there is also significant acidification from lactic acid, without the cells dying, which we are very focused on understanding,” says Christian Damsgaard.
First mice, then humans
It has long been known that birds’ retinas lack blood vessels—but it was only recently that researchers at Aarhus University discovered that there is also no oxygen present.
This forms the basis for the current research, which is still at the cellular level and therefore in its early stages. The next step will be experiments attempting to replicate some of the cellular adaptations found in the retina to see if they can be transferred to human cells.
By genetically modifying human cells, researchers can investigate whether the cells can tolerate lower oxygen levels, similar to birds.
“If we discover that, for example, a specific protein is responsible for tolerance to low oxygen, we can try to stimulate its expression in a human cell,” explains Christian Damsgaard.
The subsequent step would be experiments in mice, but it will be many years before a potential treatment could be tested in humans. Christian Damsgaard predicts that it could take decades.
“Oxygen deprivation is part of many different types of disease, especially cardiovascular diseases, so if we can find ways to improve conditions for patients, it would be extremely significant,” he says.
Fish can tolerate ten times as much oxygen
In addition to birds, Christian Damsgaard and his colleagues are also studying fish eyes.
While birds hold the key to understanding how to help patients with a blood clot, fish hold the key to helping patients after a blood clot.
“Fish have an oxygen gland behind the eye that can extract oxygen from red blood cells and release it, causing oxygen levels to rise extremely high behind the eye,” explains Christian Damsgaard.
“This drives oxygen diffusion through the fish retina, and it means that oxygen levels are ten times higher than in any other cells known.”
When a blood clot in humans is treated and dissolved, a large quantity of oxygen flows into the cells, which for a period had very limited access to oxygen.
This is problematic because it generates reactive oxygen species that damage cells in the body, explains Christian Damsgaard.
The cells in the fish retina constantly live under conditions with ten times the usual oxygen, so researchers are investigating what defence mechanisms the fish have developed to tolerate such extreme levels—without being harmed.
“The more oxygen, the more reactive oxygen species the cells produce—and these are harmful, in both fish and humans,” says Christian Damsgaard.
“But fish have developed a mechanism that prevents tissue damage at high oxygen levels. If we can determine this, we could potentially help patients after treatment for a blood clot.”
The retinas of birds and fish are therefore both highly unique and have evolved to survive under extreme conditions. The research group at Aarhus University hopes to learn from them.