NYU Langone broke new ground with a whole-eye transplant in 2023. Now it is part of a $56 million research project to advance vision-restoring transplants.
Credit: Getty Images / Nata Serenko
Retina-degenerating eye diseases such as glaucoma, macular degeneration, and diabetic retinopathy have caused irreversible vision loss for millions of people around the world. An ambitious new project aims to reverse that loss by means of a whole-eye transplant.
Science fiction? A team of more than 40 scientists, physicians, and other investigators from multiple collaborating institutions, including NYU Langone Health, believes otherwise. Transplants of the cornea, the eye’s clear outer layer, have already helped improve vision for millions of patients whose own corneas have been damaged or diseased. In May 2023, a 140-person team at NYU Langone broke new ground with a partial-face and whole-eye transplant.
During the 21-hour surgery for Aaron James, then 46, who lost his left eye and the left side of his face in a high-voltage power line accident, surgeons completed the first-ever transplant of a donor eye and its accompanying optic nerve into a human recipient. Although the surgery did not ultimately restore vision in his new left eye, a portion of its rod and cone cells, the light-detecting neurons in the retina, survived.
“It was a really big leap forward,” says , associate professor of neuroscience and of ophthalmology. “Getting the eyeball tissue to remain alive until the transplant and then stay alive in the patient is just phenomenal.”
Eduardo D. Rodriguez, MD, DDS, the Helen L. Kimmel Professor of Reconstructive Plastic Surgery, chair of the , and director of the Face Transplant Program and the Laura and Isaac Perlmutter Cosmetic Plastic Surgery Center, recalls that many experts doubted whether the team would see any signs of posttransplant eye survival. Instead, he and his colleagues published several surprising findings in the Journal of the American Medical Association, including their observations that the eye had retained its normal pressure, blood supply, and structural integrity one year after the transplant, with no signs of rejection.
“We’ve had these remarkable discoveries that no one ever expected and these eureka moments, and now we can focus in and explore that,” Dr. Rodriguez says. “I think it’s a very good takeoff point for pursuing the next steps.”
Based on these encouraging results, NYU Langone was asked to join a $56 million effort to make vision-restoring whole-eye transplants a reality. The project, awarded by the Advanced Research Projects Agency for Health (ARPA-H), a federal agency, and co-led by Stanford University and the University of Pittsburgh, is titled Viability, Imaging, Surgical, Immunomodulation, Ocular preservation, and Neuroregeneration (VISION) Strategies for Whole Eye Transplant.
Kathryn A. Colby, MD, PhD, the Elisabeth J. Cohen, MD, Professor of Ophthalmology and chair of the , says ARPA-H is known for funding ambitious projects that have the potential to be transformative. “This is indeed an audacious goal, and one that will require the combined talents of multiple specialists,” she says.
To achieve its ultimate objective of restoring sight, the team will need to complete four major steps, explains Dr. Liddelow. With its successful transplant, NYU Langone has already made considerable progress toward the first two: keeping the donor’s eye viable both before and after the surgery.
The final two steps are even more challenging. “It’s not enough simply for the eyeball to survive. There must be a mechanism that transmits the visual information from the retinal cells to the brain,” Dr. Colby says. Establishing that connection may require a new way to regenerate the optic nerve’s severed axons—the long tails of nerve cells that transmit electrical signals—or a bioengineering approach that would restore the conduit between the eye and the brain.
Regenerating axons is a painstaking process that can take months or even years. “We’re asking a tiny neuron to regenerate its axon and grow hundreds or thousands of times its own length and go to the exact right place within an environment very different from the developing brain of a baby,” explains Dr. Liddelow.
Once the eye–brain connection is reestablished, doctors still need to determine how to “turn on” the neurons to enable vision. Sight restoration requires delicate, well-coordinated, and constant communication between multiple cell types within the brain, visual system, and retina. For vision-granting neurons to work normally, researchers have learned that star-shaped cells of the central nervous system, known as astrocytes, provide essential support.
As part of the project, will receive tissue samples from other consortium members and conduct sophisticated analyses to map out the types of cells that survive an eye transplant procedure, the way the immune system responds, and how the neuron-supporting astrocyte cells behave. NYU Langone’s is particularly well suited for performing what’s known as spatial transcriptomics, which can measure the activity of genes at distinct locations within tissue samples from the retina, optic nerve, and visual cortex in the back of the brain.
The information gathered from these experiments could reveal not only the presence or absence of different cell types, but also their response to antirejection drugs and other interventions during and after the transplantation process. The data could also point to cellular markers of transplant rejection and drugs that might mitigate that risk.
“If we can provide a person who is blind with 10 percent of their vision, so that they can navigate the world more safely and independently, that would be phenomenal,” Dr. Liddelow says. “Of course, we hope to eventually achieve 100 percent perfect color vision. But the realistic early results are likely to be some portion of that vision, which would still be important progress.”
