Page 14 - Abacoa Community News - July '22

Page 14, Abacoa
Science on the cutting eDge

The Scripps Research Institute News

Light After Death: Scientists eventually resulted in this success, which we think will lead Sugared Proteins Called
to a transformative understanding of human eyesight.”
Revive Human Eyes “Revival of light signalling in the postmortem mouse Proteoglycans Start To Give
and human retina” was co-authored by Fatima Abbas, Silke
By restoring the Becker, Bryan Jones and Frans Vinberg of the University of Up Their Secrets
light-sensing function Utah; Ludovic Mure and Satchidananda Panda of the Salk
of huma n re ti nas Institute; and Anne Hanneken of Scripps Research. Scripps Research scientists develop a sophisticated
hours after death, The research was supported by, among others, the platform for building and modifying proteoglycans to
Scripps Research and National Institutes of Health (P30 EY014800, UL1 dissect their normal roles and their roles in diseases,
collaborators reveal a TR002550, EY031706, R01 EY015128, R01 EY028927), including cancers.
new way to study age- the Daro Foundation, the A. C. Israel Foundation, the Scientists at Scripps Research have developed a
related macular degeneration and other eye disorders. Warren Family Foundation, the Renaissance Charitable set of methods for the closer study of one of the least-
Scientists from Scripps Research and the University of Foundation, The Rancho Santa Fe Foundation, the Money accessible, least-understood players in biology: protein-
Utah have made the surprising discovery that the human eye Arenz Foundation, the Considine Foundation, the Fonseca sugar conjugates called proteoglycans.
can be removed from the body even hours after death and Foundation, the Pfeiffer Foundation, the Mericos Eye
the function of the light-sensing cells in the central vision Institute, and the Thomas and Audrey Pine Foundation. Scripps Research on page 15
can be revived.
The finding, reported in Nature on May 11, 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, M.D., associate
professor of Molecular Medicine at Scripps Research, and
a longtime 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, Ph.D., assistant
professor of Ophthalmology and 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 nonfunctional 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