For people who are completely blind for many reasons – genetic diseases, age-related conditions, accidents, combat injuries – often appear: Can’t I just have new eyes? Blind parents sometimes ask: Can I give my children an eye?
Eye transplants may sound simple, but until recently, it was considered a viable way to restore vision. Leading ophthalmology and medical experts quickly shut down the conversation about whole-eye transplants, as it goes far beyond the science and technology of today’s surgical community on multiple levels. It’s something from a sci-fi movie, not an operating room.
But in May 2023, the prospect of a full eye transplant changed dramatically when veterans involved in a high-voltage electric accident underwent full eye and partial face transplants from NYU Langone Health’s surgical team. Although the veterinarian has not yet recovered his sight in the transplanted eyes, the blood flow in the eyes is good, and normal pressure and its rods and cones (retinal cells that respond to vision) show light sensitivity. While vision recovery is the ultimate goal, the results of this first eye transplant are significant and groundbreaking. The complete results were held on September 9, 2024 Journal of the American Medical Association (JAMA)).
Excitingly, the Advanced Research Program (ARPA-H) launched the Human Eye Transplantation Program in January 2024 with the goal of achieving successful full functional eye movement, i.e., IE, visual recovery. ARPA-H, the federal agency of the U.S. Department of Health and Human Services, has a mission to drive transformative biomedical and health breakthroughs to provide health solutions for all.
More than one million Americans cannot compensate for bilateral vision loss due to various diseases, including age-related macular degeneration, glaucoma, and diabetic retinopathy. The universality of irreversible blindness emphasizes the enormous need for the development of vision recovery procedures.
There is no doubt that full eye movement (wet) is a highly ambitious effort. Some groundbreaking progress must be made in order to work wet.
According to the transplantation of ARPA-H’s innovative solutions for human eye transplantation, the program has three technical areas:
- Organize harvesting and preservation (TA1)
- Optic nerve reinstallation and repair (TA2)
- Surgery, postoperative care and evaluation (TA3)
Organize harvesting and preservation (TA1)
The supply of potential whole-eye transplant donor eyes is large. 70,000 Americans die every year in their eyes. Eye donors list computer networks connecting donors and recipients on the Organ Procurement and Transplantation Network (OPTN). Organ procurement tissue, surgeons, and organ transport and storage experts work together to ensure viable eye tissue is available.
However, only a portion of the eyes are used for transplantation at present. The cornea is the most commonly transplanted eye tissue, with 40,000 such transplants per year in the successful full-eye harvest and preservation in the United States, requiring new technologies to preserve the optic nerve, retina and other eye tissue. The neural tissue requires continuous oxygenation and is sensitive to nutrient loss.
The first TA1 goal is to develop technology and a solution to maintain the viability of the eyes and optic nerves in vitro, which can be used for more than 24 hours in the eyes of animals (Precursor). The retinal structure will be analyzed to ensure there are no signs of retinal detachment or corneal edema and that the retinal tissue remains healthy. The function of the retina will be evaluated by an electronic graph (ERG) that measures retinal sensitivity.
The next TA1 goal is to extend the preservation of human eyes for more than 48 hours (Precursor). The structure of the transplanted eye will be evaluated using techniques such as optical coherence tomography (OCT), magnetic resonance imaging (MRI), and degenerated retinal cells. ERG will measure retinal function.
Optic nerve reconnection and repair (TA2)
Optical nerve regeneration for vision recovery is elusive and only breakthroughs for clinical researchers working to restore mobility in patients with spinal cord injury.
The initial goal of TA2 was to develop technologies to achieve optic nerve repair/regeneration in small animal models. The new technology will include stem cells with neural encapsulation, biological symptoms and/or neurosurvival factors. Visual functions in animals will be measured by ERG, acuity test and/or a maze.
The TA2 team will then evaluate optic nerve repair/regeneration and whole-eye transplant in large animal models, with the aim of achieving at least 50% 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 the brain’s response to visual stimulation, optical motion response, and pupil light reflex.
If successful, the TA2 team will work with the TA3 surgical team to evaluate optic nerve repair/regeneration in human whole eye transplant recipients. Imaging techniques such as OCT and MRI can be used to evaluate the function of optic nerve connections. A person’s vision is intended to be measured by shape recognition, contrast sensitivity and shape recognition tests.
Surgery, postoperative care and evaluation (TA3)
Initially, the TA3 team aimed to develop microsurgery protocols for wet animals and humans. In addition to implementing optic nerve regeneration/reconnection protocols, surgeons will also develop reanalysis protocols for the vasculature, muscles 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 try to minimize receptor disfigure. Donor eye vigor will be evaluated using imaging techniques, including: OCT, MRI, CT and adaptive optics. The polyluminescence mobility test (a maze with variable light settings) will be used to evaluate visual functions in large animals.
With the success of large animals, surgeons will strive to successfully moisturize without immune rejection and sustained eye viability at least in humans. Visual features will be evaluated using Snellen eye diagrams, including the ability to large letters at distances (high magnification) distances and the ability to navigate without help. Recipients will also be asked to complete the Vision and Quality of Life questionnaire.
Transplantation results using human eye transplant
Although vision recovery is the primary goal, the potential impact of human eye transplant programs goes beyond the scope of ophthalmology. Technologies and technologies developed for eye transplantation and nerve regeneration may have significant transformation 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.
All in all, the ARPA-H program is an innovation catalyst that drives advancement in multiple medical fields, with the potential to change the lives of countless individuals rather than those with vision loss.
Author’s resume:
Dr. Chad Jackson,,,,, is a senior director of the Foundation’s Preclinical Translation Research Program for Fighting Blindness (Foundation). Dr. Jackson will manage the report and strategic plan for the ARPA-H transplant human eye transplant program on behalf of the program’s Subweapons Foundation (ARPA-H). Dr. Jackson has over 20 years of R&D experience in the field of biomedical sciences and is a champion of international scientific participation, innovation ecosystem development and entrepreneurship as a means of solving the world’s most challenging problems. Prior to joining the Foundation, Dr. Jackson supported the Office of Biotechnology at the Defense Advanced Research Projects Agency, covering topics of infectious diseases, synthetic biology, and human performance. He is currently the chairman of the board of the Seed Laboratory and is a trustee of the Board of Trustees of the University of Ellam. Dr. Jackson received his PhD in Molecular and Systems PhD from Emory University and a Bachelor of Biochemistry from Earlham College.
“This study is funded in part by the Department of Health (ARPA-H). The views and conclusions contained in this document are those of the author and should not be interpreted as representing the official policy of the U.S. government, indicating or implied.”
Photo: Jay_Zynism, Getty Images
