DOD Funded Researcher Examines Whole Eye Transplantation
Featured speaker Kia Washington, MD (University of Pittsburgh School of Medicine)
On March 29, AEVR hosted its ninth Defense-related Vision Research Congressional Briefing entitled Whole Eye Transplantation" From Experimental Model to Clinical Translation, which was co-sponsored by Research to Prevent Blindness (RPB), Blinded Veterans Association (BVA) and the Association for Research in Vision and Ophthalmology (ARVO).
The briefing featured clinician-scientist Kia Washington, MD, an assistant Professor in the Department of Plastic Surgery at the University of Pittsburgh School of Medicine, who also serves as Co-Director of the Vascularized Composite Allotransplantation and Microsurgery (VCAM) Laboratory in the Department of Plastic Surgery. She serves as Section Chief of Plastic Surgery in the VA Pittsburgh Healthcare System, and was recently named Director of a newly-established interdisciplinary research program that focuses on the science of whole eye transplantation. Funded by a National Institutes of Health (NIH) training grant originally at the Starzl Transplant Institute at the University of Pittsburgh, Dr. Washington began working with rodents as an animal model for facial transplants. Her work on facial transplants formed the basis for her later work on Whole Eye Transplantation (WET), which is funded by the Department of Defense (DOD, see box below).
Blindness caused by ocular trauma cannot be cured because of damage to the optic nerve, which is the nerve that contributes to the ability to see and is part of the central nervous system. Unlike nerves in the hands and legs, the optic nerve does not have the ability to repair itself after it is injured. The goal of Dr. Washington's research is to reverse blindness that occurs in wounded warriors through the study of WET, although potentially anyone who has lost vision could benefit from it. Similar to face and hand transplantation, the concept of WET is to restore form and function of a transplanted eye. WET offers the potential to provide viable retinal ganglion cells, which are the cells that carry visual information from the eye through the optic nerve to the brain.
Dr. Washington began the briefing by noting that the idea of transplanting an entire eye is not new—it was first proposed by a French doctor in the early 1800s, who transplanted a rabbit eye into a blind girl, a procedure which, not surprisingly, failed. Efforts to transplant entire globes in both animals and humans continued up through World War II-all without success. In 1977, a task force at the National Eye Institute (NEI) concluded that WET was not likely, due to three major impediments: inadequate blood flow to keep the organ alive; immune system rejection of the transplanted tissue; and, most importantly, lack of nerve function past the point of where the optic nerve was severed. Overcoming these three challenges has been the focus of Dr. Washington's research, which has had success in meeting the first two. But if a transplanted eye is going to restore vision, it is the third barrier that is essential to overcome.
Working with a small animal model allows the team to do multiple procedures to be able to have enough data to then attempt the procedure in humans. In research done in the 1930s and 1940s, the small animal model used were cold-blooded invertebrates, which in hindsight were not good models for warm-blooded animals like humans. Other research attempts had used dogs and sheep which were better animal models and showed results in transplanting and sustaining whole eyes, but being larger animals provided a different set of challenges. These projects were able to transplant eyes by attaching them to other parts of the animal body, and while the researchers were able to maintain blood flow sufficiently so that the tissue was kept alive, this was not going to result in a return of vision since an optic nerve connection was not established. Dr. Washingtons team has successfully transplanted complete globes from a donor animal to a recipient, and kept the tissue alive and prevented rejection. However, getting the optic nerve to regenerate and transmit signals to the brain remains elusive.
The first step was making sure that the transplant was vascularized, meaning that it had its own blood supply, and that it was orthotopic, meaning that it was located in the anatomically-correct spot on the recipient animal. Once the donated eye is transplanted into the recipient, the blood supply is connected and then the optic nerve. The team has used Optical Coherence Tomography (OCT), a non-invasive imaging technology, to examine in very small detail the structures in the eye post-transplantation to evaluate the health and function of the eye. Using a special dye injected into the eyes and MRI imaging techniques, they can see that the nerves continue to function from the eye right through to the brain in the non-transplanted eye, while in the transplanted eye the signals stop at the point where the two ends of the optic nerve were sewn together. This was expected because the researchers have not yet introduced any therapies that would help the optic nerve regenerate.
The team is testing a number of different techniques to preserve the optic nerves and encourage them to regenerate. One therapy has introduced the use of a wrap infused with special drugs that holds the two severed ends of the optic nerve together to allow the two ends to knit to the other. Also being evaluated for effectiveness are gene therapy strategies which tap into the innate ability of our body to regenerate after injury.
Finally, the team is also doing human cadaver studies, using a multi-disciplinary approach, to develop techniques to remove an eye and optic nerve from a donor cadaver and transplant the entire structure into a recipient cadaver, in order to develop the surgical protocols for doing this procedure on human subjects when the researchers are ready to move to that stage.
About Defense-related Vision Research and Dr. Washington's Funding
Since Fiscal Year (FY) 2009, when Congress first funded peer-reviewed vision research in DOD appropriations, the Vision Research Program (VRP) has awarded 77 grants for a total of $66.5 million to researchers addressing penetrating eye injuries, corneal healing, retinal/corneal protection, Traumatic Brain Injury (TBI)-related visual dysfunction, eye blast phenomenon, and vision rehabilitation, all areas addressing DOD-identified research gaps.
Dr. Washington originally received a $250,000 Hypothesis Development Award in the FY2013 VRP funding cycle for her WET research. The work done on that grant led to her project being submitted by the VRP Program Manager to the Joint Warfighter Program, (JWP), which funds projects that had previously been funded by other DOD research programs and were deemed worthy of follow-up funding to continue the work. Dr. Washington received a JWP grant for $6 million in FY2016.
This was not Dr. Washington' s first time on Capitol Hill. In October 2015, she participated in the first Emerging Vision Scientist Capitol Hill events, and was invited back to speak due to her effectiveness in describing the value of federally funded vision research.
Joe Bogart, the newly-appointed Executive Director of briefing co-sponsor Blinded Veterans Association, with Dr. Washington
Dr. Washington with Ali Manson from the American Optometric Association