Salt Lake City, Utah — Scientists have reanimated the light-sensitive neuron cells in the eyes of organ donors and restored communication between them as part of a series of discoveries that will transform brain and vision research.
Billions of neurons in the central nervous system carry sensory information as electrical signals; in the eye, specialized neurons known as photoreceptors perceive light.
Publication in Naturea team of researchers from the John A. Moran Eye Center at the University of Utah and collaborators from Scripps Research describe how they used the retina as a model of the central nervous system to study how neurons die and new ways to reanimate them.
“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 detail and color,” explains Moran Eye Center scientist Fatima Abbas, PhD, lead author of the published study. “In the eyes obtained up to five hours after the death of an organ donor, these cells responded to bright light, colored lights and even very faint flashes of light.”
While the initial experiments reanimated the photoreceptors, the cells appeared to have lost the ability to communicate with other cells in the retina. The team identified oxygen deprivation as the critical factor leading to this loss of communication.
To overcome the challenge, Scripps Research associate professor Anne Hanneken, MD, procured the eyes of an organ donor in less than 20 minutes from the moment of death, while Moran Eye Center scientist Frans Vinberg, PhD, designed a special transport unit to restore oxygenation and other nutrients to the organ donor’s eyes.
Vinberg also built a device to stimulate the retina and measure the electrical activity of its cells. With this approach, the team was able to restore a specific electrical signal seen in living eyes, the ‘b-wave’. It is the first b-wave recording made by the central retina of post mortem human eyes.
“We were able to get retinal cells to talk, as they do in the living eye to mediate human vision,” says Vinberg. “Past 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.”
The process the team demonstrated could be used to study other neuronal tissues in the central nervous system. It is a transformative technical advance that can help researchers develop a better understanding of neurodegenerative diseases, including blinding retinal diseases such as age-related macular degeneration.
The Nature the study, Revival of light signaling in the postmortem mouse and human retina, has now provided data from over 40 human donor eyes, including the first description of a mechanism that should limit the speed of human central vision.
Vinberg points out that this approach can reduce research costs compared to non-human primate research and reliance on animal models that produce results that don’t always apply to humans. Although mice are commonly used in vision research, they do not have a macula. Researchers can also test new potential therapies on functioning human eye cells, accelerating drug development.
“The scientific community can now study human vision in ways that simply aren’t possible with laboratory animals,” says Vinberg. “We hope this will motivate organ donor societies, organ donors and eye banks by helping them understand the exciting new possibilities offered by this type of research.”
Hanneken, who is also a longtime retinal surgeon affiliated with Scripps Memorial Hospital La Jolla, said the ability to produce vital patches of human retinal tissue could lead to new therapies for blinding disease.
“Until now, it has not been possible to get cells in all the different layers of the central retina to communicate with each other as they normally do in a living retina,” said Hanneken. “In the future, we will be able to use this approach to develop treatments to improve vision and light signaling in eyes with macular diseases, such as age-related macular degeneration.”
The Nature the study joins a body of science that raises questions about the irreversible nature of death, defined in part by the irreversible loss of neuronal activity. Yale University researchers made headlines when they reanimated the pigs’ disembodied brains four hours after death, but they did not restore global neuronal activity.
The study authors are: Fatima Abbas, Silke Becker, Bryan W. Jones and Frans Vinberg of the University of Utah, Ludovic S. Mure and Satchidananda Panda of the Salk Institute for Biological Studies, and Anne Hanneken of Scripps Research.
Donor eyes for the study were obtained in collaboration with Utah Lions Eye Bank, San Diego Eye Bank, and organ donor company LifeSharing. The research team is deeply grateful to those who donated their eyes and their legal representatives who welcomed the surgical team’s efforts to procure the eyes.
The research was supported by the National Institutes of Health and an Unlimited Research Grant to Prevent Blindness, New York, NY, to the Department of Ophthalmology and Visual Sciences, University of Utah.
Human tissue samples
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Revival of light signaling in the post mortem mouse and human retina
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