In a series of discoveries that could transform brain and vision research, scientists have revived the light-sensing neurons in eyes collected from post-mortem organ donors and restored their ability to communicate.
Many human organs can be transplanted from deceased donors, but tissues from the central nervous system rapidly lose their viability after circulation stops and oxygen deprivation occurs. This impedes their potential use.
The team used the retina as a model of the human central nervous system – which contains billions of neurons that transmit sensory information as electrical signals – as a way to study how neurons die and to look at potential new methods to restore them.
They’ve established a new approach, outlined in a study published in Nature, which will allow scientists to study human vision in post-mortem donated eyes.
“We were able to wake up 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 colour,” explains lead author Fatima Abbas, a scientist at the John A. Moran Eye Centre at the University of Utah in the US. “In eyes obtained up to five hours after an organ donor’s death, these cells responded to bright light, coloured lights, and even very dim flashes of light.”
In these initial experiments the team was able to revive the photoreceptors by restoring normal pH and oxygenation; however, it appeared that they had lost their ability to communicate with other cells in the retina due to oxygen deprivation.
To overcome this problem, they secured organ donor eyes in under 20 minutes from time of death, designed a special transportation unit to restore oxygenation and other nutrients to them, and another device that stimulates the retina and measures the electrical activity of its cells.
Using this approach, the team was able to restore a specific electrical signal seen in living eyes, the “b wave”, and it’s the first b wave recording made from the central retina of post-mortem human eyes.
“We were able to make the retinal cells talk to each other, the way they do in the living eye to mediate human vision,” says co-author Frans Vinberg, assistant professor of Ophthalmology & Visual Sciences at the University of Utah, US. “Past studies have restored very limited electrical activity in organ donor eyes, but this has never been achieved in the macula, and never to the extent we have now demonstrated.”
This technical advance could be used to study other neuronal tissues in the central nervous system and help scientists develop a better understanding of neurodegenerative diseases – including blinding retinal diseases such as age-related macular degeneration.
“Until now, it hasn’t been possible to get the cells in all of the different layers of the central retina to communicate with each other the way they normally do in a living retina,” says co-author Anne Hanneken, associate professor of Molecular Medicine at Scripps Research, US. “Going forward, we’ll be able to use this approach to develop treatments to improve vision and light signalling in eyes with macular diseases, such as age-related macular degeneration.”
The approach can reduce dependence on animal models that don’t always produce results that apply to humans, and now researchers can also test potential new therapies on functioning human eye cells, speeding drug development.
“The scientific community can now study human vision in ways that just aren’t possible with laboratory animals,” adds Vinberg. “We hope this will motivate organ donor societies, organ donors and eye banks by helping them understand the exciting new possibilities this type of research offers.”