Science

Researchers bring human eye cells back to life, changing our understanding of death

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Efforts to investigate diseases of the human eye and nerve function are hampered by the fact that these organs rapidly degrade after death. In addition, the eyes of animals are still different from ours. To remedy this, an international team of researchers has developed a new method to “bring back to life” retinas taken from donors 5 hours after their death. This technical achievement will enable new research into the functioning of the human eye, the nervous system, and the lifespan of transplanted organs. This success also opens up new avenues for the treatment of neurodegenerative diseases, including age-related macular degeneration.

Death is defined as an irreversible cessation of circulation, respiration, or brain activity. Many human peripheral organs can be transplanted from deceased donors using protocols to optimize viability. However, tissues of the central nervous system and some of its associated organs, such as the eyes, quickly lose their vitality after circulatory arrest, making it difficult to transplant them. Indeed, the billions of neurons in the central nervous system transmit sensory information in the form of electrical signals; in the eye, special neurons called photoreceptors capture light. These cells die quickly after cardiac arrest. However, the time course and mechanisms that cause neuronal death, as well as the possibility of reactivation, remain poorly understood.

To better understand how nerve cells succumb to the lack of oxygen caused by the cessation of general circulatory activity, a group of American and Swiss researchers used the retina as a model of the central nervous system. They measured the activity of mouse (mouse) and human retinal cells shortly after death and developed new methods for bringing them back to life. Their work has been published in the journal Nature.

Restoration of cellular communication after death

To achieve her goal, Scripps Research associate professor Ann Hanneken was able to donate more than 40 eyes from organ donors within 20 minutes of death. Meanwhile, Frans Winberg of the Moran Eye Center has developed a special transport unit to restore oxygenation and other nutrients to donor eyes, as well as a device to stimulate the retina and measure the electrical activity of its cells. Thus, the team went through two stages.

First, the researchers demonstrated a rapid decline in neuronal signaling and identified the conditions required for potential resuscitation of eye cells in vivo in mice, after death, and in the human retina. Second, they measured the reactions induced by light in the macular photoreceptors of human eyes taken from donors within 5 hours of their death. They were then able to identify modifiable factors leading to reversible and irreversible loss of light signaling after death.

While early experiments revived photoreceptors, the cells seem to have lost the ability to communicate with other retinal cells. The team identified oxygen starvation as a critical factor leading to loss of communications.

Fatima Abbas of the Moran Eye Center and lead author of the study explains in a press release: “We were able to awaken photoreceptor cells in the human macula, which is the part of the retina responsible for our central vision and our ability to see fine details and color. In eyes obtained within five hours of the organ donor’s death, these cells responded to bright light, colored lights, and even very weak flashes of light.”

Using their innovative approach to keeping cells oxygenated for longer periods of time by extending the lifetime of the retina and neuronal cells, the team was able to recover a specific electrical signal seen in living eyes, the “b wave”. The latter indicates a connection between all the layers of macular cells that allow us to see. This is the first post-mortem b-wave recording made from the center of the human retina. However, this temporary restoration of retinal cell activity does not mean that the donor eyeballs could “see”. The higher visual centers in the brain are needed to revive the whole process of vision.

Frans Winberg says: “We were able to get retinal cells to communicate, as they do in the living eye, to mediate human vision. Previous studies have restored very limited electrical activity in the eyes of organ donors, but this has never been achieved in the macula, and never to the extent that we have now demonstrated.”

In view of these results, some experts question the irreversible nature of death in the central nervous system. Indeed, if some organs of the human body can be saved for transplantation, the central nervous system ceases to function too quickly to be “rebuilt” in the perspective of transplantation. However, all the constituent elements of our nervous system do not die at the same rate, the mechanisms of “survival” are sometimes established for a while, then the concept of death becomes more complicated. In this context, the exploits described in the article will allow you to see things more clearly (no pun intended) and point to new opportunities in terms of medical advances.

Study of neurodegenerative diseases

Thus, the process demonstrated by the team could be used to study other neural tissues of the central nervous system. This will help researchers better understand neurodegenerative diseases, including blinding retinal diseases such as age-related macular degeneration.

In addition, potential treatments could be tested on functional cells from the human eye, allowing for faster development of treatments without the use of laboratory animals. Indeed, Frans Winberg notes that this approach can reduce research costs compared to working on non-human primates and relying on animal models, producing results that are not always applicable to humans. For example, although mice are commonly used in vision research, they do not have a macula, unlike us.

In addition, Ann Hanneken says that these discoveries will certainly help create viable patches of human retinal tissue to treat diseases that cause blindness. She explains: “Until now, it has not been possible to get the cells of all the different layers of the central retina to communicate with each other, as is normally the case in a living retina. In the future, we may use this approach to develop treatments to improve vision and light signaling in eyes with macular conditions such as age-related macular degeneration.”

Finally, this study joins the scientific corpus on the irreversibility or irreversibility of death. In 2018, researchers at Yale University managed to “revive” the brain of a pig 4 hours after its death, but could not restore the overall activity of neurons. The procedure was carried out according to the same scheme, that is, the restoration of blood circulation, which allows the supply of oxygen and essential nutrients. Data collected by Abbas et al. may provide valuable clues to future post-mortem experiments.

Nature

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