Scientists from Scripps Research and the University of Utah have made the surprising discovery that the human eye can be removed from the body even hours after death and the function of the light-sensing cells in the central vision can be revived.
The finding, reported in Nature on May 11, 2022, enables direct experimentation on the human retina, in a way that had been largely impossible, to better understand eye diseases and develop new ways to treat them. The study also hints that nerve cells from the central nervous system may be easier to revive after death than scientists had widely believed.
“We were essentially able to get the cells to ‘wake up’ and talk to each other after death,” says study co-corresponding author Anne Hanneken, MD, associate professor of Molecular Medicine at Scripps Research, and a long-time retinal surgeon affiliated with Scripps Memorial Hospital La Jolla. “We’re hoping that this new ability to revive the central human retina and study it directly in the laboratory will lead to a much better understanding of human vision and better care for the millions of patients with retinal diseases.”
“The scientific community can now study human vision in ways that just aren’t possible with laboratory animals,” says corresponding author Frans Vinberg, PhD, assistant professor of Ophthalmology & Visual Sciences at the University of Utah’s John A. Moran Eye Center, who also holds an appointment as a visiting investigator at Scripps Research. We hope this will motivate scientists to work with organ donor societies and eye banks to build collaborations that will lead to exciting new research discoveries.”
The retina is a highly sensitive system that is prone to deterioration due to inherited gene mutations or age-related conditions, including diabetes and age-related macular degeneration. It is estimated that more than 10 million older Americans have retinal degenerative diseases. Current treatments can ameliorate but cannot cure these diseases.
The shortcomings of current treatments are due in part to the obstacles researchers typically face when studying retinal diseases. The retina of the mouse—the standard lab animal—is quite different from the human retina. Moreover, prior studies from deceased organ donors are scarce. Most researchers believe that human retinal neurons become swiftly non-functional after death.
In the study, researchers confirmed this rapid loss of retinal function in mice, using a method called electroretinography (ERG) to track the decline in retinal neuron activity in the minutes after death. However, they found that if they removed the eyes after death and then restored oxygen and a normal acid-alkaline (pH) balance, the retinas largely revived. There was light-responsive electrical activity in retinal neurons called photoreceptors, and there was evidence of photoreceptor signaling to other retinal neurons, known as bipolar cells and retinal ganglion cells, that constitute the next stage of visual signal processing.
The researchers could revive light-signaling in mouse photoreceptors up to three hours after death. Surprisingly, the scientists found that they could obtain similar retinal signaling from human autopsied eyes when they were removed up to five hours after death.
To enable these experiments, Hanneken collected tissues with the help of the San Diego Eye Bank and the organ donor society Lifesharing and optimized the surgical recovery of the human eyes. Vinberg used his biomedical and electrical engineering background to design a transportation unit to restore the oxygenation of the organ donor eyes and build the ERG device to stimulate and measure the retina.
Overall, researchers say, the experiments generated an unprecedented trove of data on the physiology of human vision. The techniques they developed also offer a new way to study the retina in health and disease—and to test drugs, retinal patch transplants, and other strategies against retinal ailments.
“One unique aspect of this study was the highly collaborative work from people and organizations that started about five years ago and persisted,” says Hanneken. “We spent years getting no light signals at all from human eyes. It was perseverance through lots of failures that eventually resulted in this success, which we think will lead to a transformative understanding of human eyesight.”
“Revival of light signalling in the postmortem mouse and human retina” was co-authored by Fatima Abbas, Silke Becker, Bryan Jones and Frans Vinberg of the University of Utah; Ludovic Mure and Satchidananda Panda of the Salk Institute; and Anne Hanneken of Scripps Research.
The research was supported by, among others, the National Institutes of Health (P30 EY014800, UL1 TR002550, EY031706, R01 EY015128, R01 EY028927), the Daro Foundation, the A. C. Israel Foundation, the Warren Family Foundation, the Renaissance Charitable Foundation, The Rancho Santa Fe Foundation, the Money Arenz Foundation, the Considine Foundation, the Fonseca Foundation, the Pfeiffer Foundation, the Mericos Eye Institute, and the Thomas and Audrey Pine Foundation.
