A research team co-led by a physician affiliated with Scripps Memorial Hospital La Jolla has demonstrated the ability to revive the retina in human organ donor eyes after death and to restore light signaling and cell communication within the central vision.
Published May 11 in the peer-reviewed journal Nature, the findings open important new research opportunities that could eventually benefit patients with age-related macular degeneration, an eye disease of the retina affecting the central vision. It is the leading cause of severe, permanent vision loss in people 60 and older.
The research was headed by two co-principal investigators: Anne Hanneken, MD, a retinal surgeon on the medical staff at Scripps La Jolla and associate professor of molecular medicine at Scripps Research, and Frans Vinberg, PhD, an electrophysiologist and assistant professor of ophthalmology and visual sciences with the University of Utah. A team from the Salk Institute, led by Satchin Panda, PhD, collaborated on the research.
“These findings will fundamentally change the way vision scientists study human eye disease going forward, because we won’t have to rely only on small animal models whose retinas are structurally different from humans,” Dr. Hanneken said. “We can use this new knowledge to study diseased patches of human retina, so we can understand where the roadblocks are, and design and test novel treatments that can potentially restore some of the dim light responses.”
In the study, researchers were able to revive the light signaling in the central vision, from one side of the retina where light is absorbed, all the way through the nerve pathways that process vision, and up to the far end of the inner retina. In addition to restoring widespread light signaling from the delicate nerves that absorb light, researchers also achieved good communication and transmission between cells across a wide spectrum of the retina.
Researchers examined the revived human donor eyes using a specialized device called an ex vivo electroretinogram, or ERG, which allows recordings of light signals in patches of retina outside of the living eye. It measures the light-evoked electrical signals in the retina similarly to how electrocardiograms measure electrical responses of the heart. Researchers placed human donor retina patches in the ERG device, stimulated the retina with various wavelengths of light, and measured the light responses from one side of the retina to the other.
“Until now, it hasn’t been possible to get the light responses in all of the different nerve layers of the central retina to communicate with each other the way they normally do a living retina,” Dr. Hanneken said. “Going forward, we’ll be able to use this approach to develop treatments that improve vision and light signaling in unhealthy eyes.”
She noted that past studies have restored very limited electrical activity in the peripheral retina of deceased donor eyes, but it has never been achieved in the central vision and never to the broad extent demonstrated in this study.
The Nature article also describes the team’s earlier, foundational work with mice models, which helped them understand the timeframe when light sensitivity decreases after death; the mechanisms that cause visual signaling to turn off after death; and parameters that allow restoration of vision after death. They found that altering parts of the eye’s environment after being recovered, such as oxygen concentration and acidity of the solution in which it was placed, was required for revival after extended postmortem times. These learnings helped inform the team’s subsequent work with human donor eyes.
Dr. Hanneken was responsible for organizing the research effort, which began about five years ago as a way to gain a better understanding of what causes visual defects in age-related macular degeneration and grew in scope as developments progressed. She also recovered the majority of the eyes used in the study from deceased organ donors at various Scripps hospitals across San Diego County. The Mericos Eye Institute at Scripps La Jolla also supported early phases of this research.
According to Dr. Hanneken, the success of reviving electrical signals in the central vision of human donor eyes will allow researchers to consider the next set of challenges that lie ahead. “This will enable scientists to study and identify roadblocks causing poor vision in humans,” she said. “Once they identify roadblocks, they can design treatments to bypass them and restore light sensitivity in the eye.”
She said this breakthrough enables scientists to think more about challenges related to the potential development of macular patch grafts in humans in the future. “There are still tremendous obstacles to performing macular patch grafts, including the critical issue of getting synapses to grow and connect the patch to the retina in the recipient.”
The research was funded by a combination of grants from the National Institutes of Health and various charitable foundations, as well as philanthropic contributions from individuals.