By Lisa A. Goldstein
To make whole eye transplants that restore sight a reality, the Department of Ophthalmology at the University of Pittsburgh is part of a project team for a program called Transplantation of Human Eye Allografts, or THEA.
The project will receive an award of up to $56 million from the Advanced Research Projects Agency for Health (ARPA-H), an agency within the U.S. Department of Health and Human Services. Pitt will likely receive around $9 million for its role in the project, the largest Pitt has received for optic nerve regeneration.
“It’s a very audacious project to have a living functional human eye transplant in a patient and then the patient has functional vision after the surgery,” said John Ash, vice-chair and director of research, Department of Ophthalmology. “A successful eye transplant has occurred already, but it’s not functional, so the eye can’t process images and connect to the brain. We want to extend that and go into the next step where we get the eye to reconnect to the brain.”
Jeffrey Goldberg, chair of ophthalmology at the Byers Eye Institute at Stanford University, will be the primary investigator leading more than 40 doctors, researchers, and industry experts from around the country. José-Alain Sahel, ophthalmology chair at the University of Pittsburgh, will colead.
“This group of people have been working for decades now on figuring out how to promote optic nerve regeneration and retinal neuron survival in diseases like glaucoma and countless 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.”
Sahel praised the strong collaborations necessary for scientific breakthroughs. “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 a whole eye transplant.”
This work is not anything new for Pitt, as this project simply taps into what the Department has already been doing.
The major hurdle is removing the eye from a donor and preserving it for up to 48 hours so that it can be collected and processed before being matched with the donor recipient. Hence, the first phase of the project is removal and preservation, which is being done by a team at Pitt led by Leah Byrne, Ethan Rossi, and Shauhua Pi with Sahel. They will also measure its functioning and survival. This is the THEA program’s technical area 1.
Technical area 2 is looking at different ways to stimulate the eye. “We can stimulate the eye to regrow ganglion cell nerve fibers to go from the retina all the way to various targets in the cellular system,” Ash said. A large group of people at Pitt including Ash, Larry Benowitz, Kun-Che Chang, Takaaki Kuwajima, Boris Rosin and Tonya Stefko are looking at various strategies to apply to ganglion cells so they survive when the optic nerve is cut. The goal is to stimulate them to grow into the reconnected optic nerve, and then the cortex, where they will allow functional vision. Ian Sigal, director, Image Acquisition and Analysis Core Module, Ophthalmology and Visual Sciences Center, Kuwajima and Stephen Badylak, from the McGowan Institute for Regenerative Medicine, are looking at ways to develop nerve wraps to allow the two ends of nerve fibers to align and then regrow. At least six members of the group at Pitt are involved in this part of optic nerve regeneration, the largest single group.
Technical area 3 involves implanting an eye into animals or patients and then getting the other components to work, like reconnecting to the blood vessels and reconnecting the nerves. To do this, the immune system must be blocked to prevent rejection. Heath Skinner, chair and medical director of Radiation Oncology Clinical Networks, Department of Radiation Oncology at Pitt, specializes in tissue and transplant rejection. He will look at ways to apply appropriate immune suppression to block tissue rejection. Walter Schneider, professor of psychology at Pitt, will look at mapping the structure of the optic nerve so it can be determined whether once reconnected and regrown, if the entire structure of the optic nerve from the back of the eye all the way into the cortex needs to be regenerated. All technical area groups will work concurrently.
“It’s really an ambitious project,” Ash said. “It’s hard to say whether we’ll have final success at the end. We will definitely make a lot of progress in understanding how to keep ganglion cells alive and functioning. We will make very good progress on where we currently stand in how to promote axon regeneration. If we get to a certain point–such as achieving through the second technical area–the chances of succeeding in an actual transplant go up dramatically.”
Images: ARPA-H