A federal funding agency that supports high-impact research capable of driving biomedical and health breakthroughs has awarded up to $47 million for a project aimed at moving eye transplants to restore vision closer to reality. The six-year award from the Advanced Research Projects Agency for Health (ARPA-H) Transplantation of Human Eye Allografts (THEA) program is intended to supercharge an interdisciplinary effort to bring eye transplantation forward to clinical trial.
To date, only one whole-eye transplant has ever been successfully performed. The experimental procedure was part of a face transplant operation by NYU Langone Health surgeons in 2023. While the transplanted eye was still viable one year later, the organ has not yet provided sight.
The USC Roski Eye Institute at the Keck School of Medicine of USC is one of eight organizations leading the project, known as Total Human Eye-allotransplantation Innovation Advancement (THEIA). The team, led by Kia Washington, MD at the University of Colorado Anschutz Medical Campus, includes Cedars-Sinai Medical Center in Los Angeles, the Foundation Fighting Blindness, Indiana University, Johns Hopkins University, the National Eye Institute and the University of Wisconsin–Madison.
The project's research strategy includes components aimed at preserving donated eyes to ensure they are viable for transplant, attaching and repairing the optic nerve, and determining the logistical and technical details of the whole procedure through post-operative care. The approach to pursuing this project encompasses cutting-edge technologies, including cell-based and gene-based therapies, as well as devices for augmenting activity in nerves that USC's team will direct.
Kimberly Gokoffski, MD, PhD, a neuro-ophthalmologist and surgeon-scientist at the Keck School of Medicine is leading USC's part of the endeavor.
"Until ARPA-H created the opportunity, the concept of eye transplantation felt too sci-fi, too out of reach, for many," said Gokoffski, a Dean's Associate Professor of Clinical Ophthalmology at the medical school and Associate Director for Research at the USC Institute for Technology and Medical Systems, a joint initiative of the Keck School of Medicine and USC Viterbi School of Engineering. "However, because of recent medical and scientific advancements, a lot of us began to realize that this was something worth pursuing."
Convening the right expertise for this challenge required bringing together a unique blend of academic medical centers, a private foundation and a government institute. Researchers in THEIA are already far along in developing the technologies and techniques involved.
Gokoffski plays a leadership role in two THEIA target areas: advancing a system for directing nerve growth with electrical stimulation; and creating the protocols for identifying suitable donors and patients, performing the eye transplant procedure and aftercare.
"There's a lot of work to be done, for instance, optimizing the balance of what you preserve in the patient and what you harvest from the donor," she said.
To accomplish these targets, Gokoffski has assembled a team of researchers from USC and the University of California, Irvine. The members represent a diverse array of disciplines: ophthalmology, neurosurgery, neurobiology and bioengineering. The team includes Gianluca Lazzi, PhD, the director of the USC Institute for Technology and Medical Systems, Mark Humayun, MD, PhD, the inventor of an FDA-approved "bionic eye" device for restoring vision, and Arthur Toga, PhD, a world-renowned expert in brain imaging.
Engineers and biologists and clinicians all think differently, and we're understanding the importance of convergent research linking different schools of thought. Interdisciplinarity is a strength at USC, and something we hope to capitalize on. We also have a tradition of success and excellence -; researchers with experience taking a technology literally from concept to the operating room -; and that tradition is backing us up."
Kimberly Gokoffski, MD, PhD, neuro-ophthalmologist and surgeon-scientist, Keck School of Medicine
She has also partnered with companies such as Neurotech, which produces an implant that releases growth factors, and Boston Scientific, whose brain implants are currently used to treat a number of neurologic conditions. For Gokoffski, engaging partners in industry is integral to accelerating progress.
"I don't consider this to be an exploratory or discovery award but rather a chance to demonstrate efficacy," she said. "We're taking what we know works and trying it out in combination with advances made by other experts in the field. I wanted to find collaborators most likely to help translate the science to the clinic, as fast as possible."
The electrical stimulation for directing nerve growth would come from a series of devices implanted in the eye and the brain. One key node would be a cuff around the area where donated and host tissue meet. The idea is to not only apply an electric field but also deliver biologic treatments that support nerve survival and minimize inflammation. This technology will take advantage of the native ways in which the body uses electricity to transmit information and guide wound healing.
"If you only drive growth of neurons from within, it's kind of like hitting the gas without controlling the steering," Gokoffski said. "The electric fields do provide gas, but they primarily provide the steering cue. Our research essentially aims to use natural cellular responses to electric fields to guide the nerves to grow to where they need to grow. If we rewire improperly, patients could experience visual confusion."
Once the preclinical work has been completed, the USC Roski Eye Institute will recruit and enroll potential patients. Gokoffski will then connect with Dr. Darrin Lee, MD, PhD, a neurosurgeon and Associate Director of the Neurorestoration Center at USC, Dr. Kia Washington and other plastic surgeons from CU Anschutz, and transplant surgeons from Cedars-Sinai to perform the eye transplantation and post-operative care at Cedars-Sinai. Follow-up assessments will occur at the USC Roski Eye Institute.
Gokoffski adds that the path from the lab to the clinic will undoubtedly call for additional collaborations. Future partners may include philanthropists interested in contributing to the restoration of sight and investors interested in bringing component technologies to the market.
"To achieve the biggest goals, we really need to join together and pool our resources," Gokoffski said. "Bringing people together to achieve a big goal is exactly what ARPA-H is trying to do."
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