For people who are completely blind from myriad causes – genetic diseases, age-related conditions, accidents, combat injuries – the question often arises: Can’t I just get a new eye? Parents of blind children sometimes ask: Can I just give my kid one of my eyes?
Transplanting an eye sounds so simple, but until recently, it wasn’t considered a feasible approach to restoring vision. Leading ophthalmology and medical experts quickly shut down the conversation about whole eye transplantation because it has been, on multiple levels, well beyond the science and technologies available today to the surgical community. It was the stuff of science fiction movies – not operating rooms.
However, in May 2023, the prospects for whole eye transplantation changed dramatically when a military veteran involved in a high-voltage electrical accident received a whole eye and partial face transplant from a surgical team at NYU Langone Health. Though the vet hasn’t regained sight in the transplanted eye, the eye has good blood flow, normal pressure, and its rods and cones – the retinal cells that respond to light for vision – are showing light sensitivity. While vision restoration is the ultimate goal, the results for this first-ever eye transplantation were remarkable and groundbreaking. Complete results were published September 9, 2024, in the Journal of the American Medical Association (JAMA).
Excitingly, the Advanced Research Projects Agency for Health (ARPA-H) launched the Transplantation of Human Eye Allografts program in January 2024 with the goal of achieving successful whole functional eye transplantation, i.e., vision restoration. ARPA-H, a federal agency within the U.S. Department of Health and Human Services, has the mission of driving transformative biomedical and health breakthroughs to provide health solutions for all.
More than one million Americans are irreparably blind with bilateral vision loss due to a variety of conditions including the common diseases age-related macular degeneration, glaucoma, and diabetic retinopathy. The prevalence of irreversible blindness underscores the tremendous need for the development of vision-restoring procedures.
Make no mistake: whole eye transplantation (WET) is a highly ambitious effort. Several groundbreaking advancements must be made for WET to work.
According to the ARPA-H Transplantation of Human Eye Allografts Innovative Solutions Opening, the program has three technical areas:
- Tissue Harvest and Preservation (TA1)
- Optic Nerve Reattachment and Repair (TA2)
- Surgery, Post-Op Care, and Assessment (TA3)
Tissue harvest and preservation (TA1)
The supply of donor eyes for potential whole eye transplantation is substantial. 70,000 Americans donate their eyes for transplantation annually upon their deaths. Eye donors are listed on the Organ Procurement and Transplantation Network (OPTN), a computer network connecting donors and recipients. Organ procurement organizations, surgeons, and organ transportation and storage specialists work together to ensure availability of viable ocular tissue.
However, only a portion of the eye is used currently for transplantation. Corneas are the most frequently transplanted ocular tissue with 40,000 such transplants performed annually in the U.S. Achievement of successful whole eye harvest and preservation requires new techniques for preserving the optic nerve, retina, and other ocular tissues. Neural tissues require continual oxygenation and are sensitive to loss of nutrients.
The first TA1 objective is to develop technology and a protocol for preserving eye and optic nerve viability outside the body for more than 24 hours in animal eyes (ex vivo). Analysis of the retinal structure will be performed to ensure there are no signs of retinal detachment or corneal edema and that the retinal tissue remains healthy. Function of retinas will be evaluated through electroretinograms (ERGs) which measure retinal sensitivity.
The next TA1 objective is to extend preservation of human donor eyes for more than 48 hours (ex vivo). The structure of the transplanted eyes will be evaluated using techniques such as optical coherence tomography (OCT), magnetic resonance imaging (MRI), and detection of degenerated retinal cells. ERGs will be performed to measure retinal function.
Optic nerve re-attachment and repair (TA2)
Vision-restoring optic nerve regeneration has been elusive and would alone be a breakthrough for ophthalmology and neurology communities, including those clinical researchers working to restore mobility to people with spinal cord injuries.
The initial objective for TA2 is to develop technologies to achieve optic nerve repair/regeneration in a small animal model. The new technologies will include stem cells with nerve wraps, bio-scaffolds, and/or neural survival factors. Visual function in the animals will be measured by ERGs, acuity tests, and/or a maze.
The TA2 teams will then evaluate optic nerve repair/regeneration and whole eye transplantation in a large animal model with the goal of achieving at least 50% of normal (baseline) optic nerve regeneration and reconnection. Retinal function and connection to the brain will be evaluated by tests such as visual evoked potentials, which measure how the brain responds to visual stimuli, optical motor responses, and pupillary light reflexes.
If successful, the TA2 teams will then work with the surgical teams for TA3 to evaluate optic nerve repair/regeneration in human whole eye transplant recipients. Imaging technologies such as OCT and MRI may be used to evaluate the function of the optic nerve connections. The human recipients’ vision intends to be measured through shape recognition, contrast sensitivity, and shape recognitions tests.
Surgery, post-op care, and assessment (TA3)
Initially, the TA3 teams aim to develop microsurgery protocols for WET in a large animal and humans. In addition to implementing the protocol for optic nerve regeneration/reconnection, the surgeons will develop protocols for reattachment of vasculature, musculature, and peripheral nerves.
One or more protocols will be developed to minimize post-op inflammation and rejection for at least six months. Surgeons will also attempt to minimize recipient disfiguration. Donor eye viability will be evaluated using imaging technologies including: OCT, MRI, CT, and adaptive optics. A multi-luminance mobility test, a maze with variable light settings, will be used to evaluate visual function in the large animals.
With success in large animals, the surgeons will strive for successful WET with goals of no immune rejection and sustained eye viability for at least one year in humans. Visual function will be assessed using a Snellen eye chart including the ability to see (with high magnification) large letters at a distance and the ability to navigate without assistance. Recipients will also be asked to complete a vision and quality-of-life questionnaire.
Leveraging transplantation of human eye allografts results
While vision restoration is the main goal, the scope of the Transplantation of Human Eye Allografts program’s potential impact transcends ophthalmology. The technologies and techniques developed for eye transplantation and nerve regeneration may have significant translational potential for other biomedical needs including: spinal cord injury, central nervous system regeneration, retinal cell and tissue transplantation, and other forms of organ and tissue transplantation.
In summary, this ARPA-H program serves as a catalyst for innovation, driving advancements in multiple fields of medicine with the potential to transform the lives of countless individuals beyond those with vision loss.
Author bio:
Chad Jackson, Ph.D., is the Senior Director of the Preclinical Translational Research Program at the Foundation Fighting Blindness (the Foundation). Dr. Jackson will manage reporting and strategic planning for ARPA-H’s Transplantation of Human Eye Allografts program on behalf of the Foundation, a subawardee of the program. Dr. Jackson has more than 20 years of research and development experience in biomedical sciences and is a champion for international science engagement, innovation ecosystem development, and entrepreneurship as a means to solving the world’s most challenging problems. Prior to joining the Foundation, Dr. Jackson supported the Defense Advanced Research Projects Agency’s Biological Technologies Office covering topics that span infectious disease, synthetic biology, and human performance. He currently serves as the chair of the board for Seeding Labs and is an Earlham College board trustee member. Dr. Jackson received his Ph.D. in Molecular & Systems Pharmacology from Emory University and a B.A. in biochemistry from Earlham College.
“This research was funded, in part, 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 U.S. Government.”
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