UPMC at the Forefront of Eye Transplantation
by Florence Kwok
Researchers at the University of Pittsburgh are bringing the possibility of “an eye for an eye” closer and closer to a reality. While not exactly in the context the saying suggests, the prospect of a whole-eye transplantation has the potential to help over 37 million people worldwide that are affected by vision loss. The condition often occurs due to one of two leading causes: macular degeneration or glaucoma.
Macular degeneration is categorized by the chronic deterioration of the macula, which is at the center of the retina found in the back of the eye. This degeneration can impair the ability to see straight and perform simple daily tasks such as reading and driving. Glaucoma, on the other hand, is a group of eye diseases characterized by problems with the optic nerve. In this case, blindness is caused by ineffective transmission of images from the eye to the brain.
While these causes for macular degeneration and glaucoma are not definite, as they are primarily gene related, symptoms can be an indication depending on factors including age, race, iris color, obesity, smoking habits and diet. The primary issue with these eye diseases is that they can go undetected in patients until after it is too late to treat. The damage is often irreversible and no amount of surgery can repair every connection the nerves once had with the brain.
New funding for the University of Pittsburgh School of Medicine has the potential to repair these nerves by making whole-eye transplantations a reality. In January 2015, the school was awarded $1.25 million by the U.S. Department of Defense Vision Research Program. Funding was granted for collaboration with clinicians and researchers from Harvard Medical School and the University of California, San Diego in order “to establish the groundwork for the nation’s first whole-eye transplantation program.”
Dr. Joel Schuman, Chair of the Department of Ophthalmology at the University of Pittsburgh School of Medicine and the Director of the UPMC Eye Center, is the co-principal investigator of the project. “The idea at first was kind of crazy,” Schuman said. “But then you break it down: the immunology, the transplant of the whole eye, and regeneration of the optic nerve, then you realize…we know how to approach the problem with optic nerve regeneration, therefore it is indeed possible.”
The risks for eye transplantation are incredibly high. Immune rejection, infection of the optic nerve and failed re-establishment of connection from the optic nerve to the vision centers of the brain can cause immediate vision loss in the patient. In fact, in 1977, a 17-member advisory council of the National Eye Institute was called for a “limited and thoughtful laboratory effort” addressing the possibility of a full eye transplantation. They acknowledged that “at present, any effort to transplant a mammalian eye is doomed to failure by the ganglion cell axon’s inability to withstand cutting, by the difficulty of insuring adequate circulation of blood to the transplanted eye during or shortly after operation, and lastly by immune rejection of foreign tissue.” As a result, researchers must rely on animal models to perform multiple experimental tests and the risks are still quite large. “The biggest risk is that it doesn’t work so that we can’t regrow the nerve,” continues Dr. Schuman. “Or that it does work in animals but doesn’t work in other animals or humans. The risk of failure is great, we can fail at a number of different points.”
Looking back, the University of Pittsburgh began exploring options for increasing the survival of retinal ganglion cells in 2009. To date, researchers have succeeded in eliminating the challenge of immunologic rejection by performing a full eye transplantation in rats matched to genetically identical donor animals. The transplanted eye within the rat remained functional for a month. However, despite fully restored circulation and connection of the optic nerve to the rat, its neurons were unable to grow back under original conditions. Though the eye had displayed healthy retinal tissue, the optic nerve was not entirely regenerated for performance. Tests revealed the impaired sensory ability of the transplanted eye, as the rat’s vision was tunneled, cloudy and its reactions were delayed.
Since this discovery, progress has been made and discussed by Schuman during a conference held at the Louis J. Fox Center for Vision Restoration of UPMC. Research efforts have found that “optic nerve generation has improved in mammals” and three percent of the formed nerve tissue connection in mice was transgenic, or formed with artificially introduced DNA, without incorporation of DNA from other animals. This advancement not only quantifies the result, but also opens the possibility of eye transplantation within humans. “This is an aggressive program with very high-risk and high-reward scenarios,” Schuman says. “We’re excited to be leading the project and honored to be collaborating with global leaders in optic nerve regeneration.”
The team at the University of Pittsburgh is optimistic. “Everything is going pretty well and in accordance with standard laboratory procedure,” Schuman said. “We are currently building a model that works for surgical transplantation in rats. Our next step is to test that in rats and see whether you have an immune response, then move the model into a large animal, like what Vijay works on, and explore the methods of optic nerve regeneration.” Dr. Vijay Gorantla, an Associate Professor of Surgery in the Department of Plastic Surgery at the University of Pittsburgh agrees: “Until recently, eye transplants have been considered science fiction. People said it was crazy, bonkers.” However, Vijay continued, "with what we now know about transplantation and, more importantly, nerve regeneration, we are finally at the point where we can have real confidence that this is something that actually can be pursued and eventually achieved.”
Dr. Kia Washington, principal investigator of this study, said that “this ongoing project may eventually lead to restoration of vision after trauma or degenerative disease.” The consortium involves a large number of institutions and assembling this team was an enormous leap. Now, with the necessary funding to support the work, the possibility of eye transplantations for the near future appears in sight. “JFK said in the early 1960s that we would reach the moon in a decade. I think it will take more than a decade,” said Schuman in regards to the future of eye transplantations. “We have a goal, and the goal is theoretically achievable. Along the way, I think there are things we will be able to achieve in other areas of transplantations and approaches to diseases, just like we did the moon.”