Zhao Joins Project To Make Whole Eye Transplants a Reality

Carnegie Mellon University is part of a major undertaking that will bring together more than 40 scientists, doctors, and industry experts hand-picked from around the country to make vision-restoring whole eye transplants a reality.

"This effort exemplifies the collaborative spirit and cutting-edge innovation required to tackle such a complex biomedical challenge," said Leon Zhao, Eberly Family Associate Professor of Biological Sciences and a member of Carnegie Mellon's Neuroscience Institute.

Dr. Jeffrey Goldberg, Blumenkranz Smead professor and chair of ophthalmology at the Byers Eye Institute at Stanford, will serve as principal investigator. Dr. José-Alain Sahel, professor and chair of the Department of Ophthalmology at the University of Pittsburgh, will co-direct the initiative with Goldberg.

"This group of people have been working for decades now on figuring out how to promote optic nerve regeneration and retinal neuron survival in glaucoma and other blinding diseases," Goldberg said. "That positions this group of collaborators to be the best situated to take on optic nerve regeneration and neuronal cell survival in the context of eye transplant."

The award of up to $56 million is from the Advanced Research Projects Agency for Health (ARPA-H) Transplantation of Human Eye Allograftso (THEA) program, led by Stanford and Pitt. The awarded project title is Viability, Imaging, Surgical, Immunomodulation, Ocular preservation and Neuroregeneration (VISION) Strategies for Whole Eye Transplant — a reflection of the breadth of the collaboration assembled to solve such a complex challenge.

"Scientific breakthroughs are impossible without strong collaborations," Sahel said. "By combining the deep knowledge about ophthalmology, tissue preservation and regeneration, immunology, and surgery of world-class scientists at Byers Eye Institute, University of Pittsburgh, and consortium members from top institutions, we are well-positioned to set the foundational steps toward restoring vision using whole eye transplant."

The biggest challenge the team will face is moving whole eye transplants from aesthetic to functional by figuring out how to regenerate the optic nerve, which connects the eye to the brain.

The 'whole' plan

The VISION for Whole Eye Transplant project is holistic in every sense of the word.

The team is made up of a potent mix of expertise and skill, which will be needed as they simultaneously advance and create cutting-edge medical devices, artificial intelligence integrations, new surgical techniques, regenerative medicine breakthroughs and rejection mitigation. The group will work dynamically, sharing information in real-time and pursuing the most promising leads.

Meticulous donor eye selection, advanced ocular imaging and specialized logistics in organ procurement and preservation will also be critical for success, and collaborators on this team are already the established leaders in these key areas of transplant science. In the end, tailored post-care rehabilitation for eye recipients will also be needed to set patients on the right track.

Amid the technical details, accessibility plays a major role in the plan.

While whole eye transplants are the north star of the three-phase, six-year project, the effort will undoubtedly bring with it more breakthroughs along the way, and that is just as exciting, Goldberg said.

"As we develop a series of new technologies that could be vision restorative in THEA and also in the many patients with glaucoma and other eye diseases, we'll leverage all the proper channels to ensure new drugs, gene therapies, and devices can be accessible to all," he said.

Carnegie Mellon contribution

Zhao is part of the team working to make whole eye transplants a reality through mapping optical nerve fibers.

The Zhao Biophotonics Lab at Carnegie Mellon will apply its Magnify Expansion Microscopy technology to addresses a critical challenge in whole eye transplantation: the precise mapping and reconstruction of optic nerve fascicles (arrangements of fibers) to corresponding layers in the lateral geniculate nucleus (LGN), located in the thalamus deep within the brain.

"This is a pivotal step toward enabling functional vision restoration in animal models and, eventually, human patients," Zhao said.

Zhao's team will provide nanoscale tissue structure resolution through physical expansion up to 11 times, retaining proteins, lipids and nucleic acids within the expanded gels. Through the process, samples are embedded in a swellable hydrogel that homogenously expands to increase the distance between molecules allowing them to be observed in greater resolution.

The innovative technique allows visualization of the intricate architecture of the optic nerve and LGN at resolutions approaching 25 nanometers using conventional microscopes and as fine as 15 nanometers when paired with advanced imaging modalities.

"Our team will produce a detailed, high-resolution map of the optic nerve's 200+ fascicles, which collectively house over a million axons," he said. "This mapping will guide the reconnection of donor and recipient optic nerves with unprecedented precision, a critical milestone in making functional whole-eye transplantation a reality."

The Carnegie Mellon collaborators also will collaborate closely with the broader project team to analyze and interpret the data, ensuring it aligns with the overall goals of the THEA program.

This research was, in part, funded by the Advanced Research Projects Agency for Health (ARPA-H). The views and conclusions contained in this document are those of the authors and should not be interpreted as representing the official policies, either expressed or implied, of the United States Government.