There are treatments and procedures for glaucoma and cataracts, such as cataract removal or eye drops and laser treatments, that can help preserve vision. The trouble is, once vision is lost it can’t be restored—yet. Two research projects are working to change that fact. One project under the auspices of the Advanced Research Projects Agency for Health (ARPA-H), an agency within the U.S. Department of Health and Human Services, has awarded $125 million to four organization working to successfully transplant human eyes. Another project is taking place at the University of Connecticut School of Medicine, where scientists have found a way to regrow optic nerves in mice, which could lead to treatments for humans.
Transplantation of Human Eye Allografts Program
Organ transplantation—such as of the kidney, liver, or skin—has helped to improve health outcomes for millions of people worldwide. One of the few organs that can’t be transplanted is the human eye. The Transplantation of Human Eye Allografts (THEA) funded by ARPA-H, is helping other organizations to make eye transplantation a reality.
Teams chosen by the agency will test and evaluate different therapies that regenerate cranial nerves, maintain important structures such as the retina and the optic nerve, and prevent inflammation or rejection. To develop successful eye transplant procedures, the THEA program will utilize microsurgical techniques, as well as genetic and cell-based therapies to preserve or regrow nerves from the eye to the brain.
The program will focus on three technical areas:
1. The successful retrieval of donor eyes and maintaining their health until transplantation;
2. Optic nerve repair and regeneration;
3. Development of surgical procedures, post-operative care protocols, and methods to assess post-operative visual function.
The organizations involved in the program are:
• InGel Therapeutics (Allston, MA): This company will develop 3D-printed click-lock gel technology with scaffolds containing stem cell-derived retinal cells.
• Stanford University: Scientists will focus on procuring donor eyes, developing strategies to support the survival and regeneration of transplanted cells, and performing the transplant surgeries.
• University of Colorado Anschutz Medical Campus: Researchers will create stem cell and bioelectronic technologies to promote nerve regeneration and perform transplant surgeries.
• University of Miami Bascom Palmer Eye Institute: Scientists will focus on donor eye procurement and preservation using its Extracorporeal Membrane Oxygenation (ECMO™) device.
The expectation is that these organizations will create new treatments for vision diseases such as glaucoma, macular degeneration, and diabetic retinopathy—conditions for which there are currently no cures. Another benefit of THEA is that its advancements in nerve regeneration for eye transplantation could also contribute to treatments for other neurological conditions, such as spinal cord injuries.
Optic Nerve Regeneration
In addition to efforts to successfully transplant eyes, research is also being done on regenerating the optic nerve. Scientists at the University of Connecticut School of Medicine have managed to regrow severed optic nerves in mice from the damaged area to the optic chiasm in the brain. The optic chiasm is the first place in the brain that the optic nerve touches, and it plays a key role in sensing light and regulating daily body rhythms.
Blunt trauma from accidents, such as car crashes, can lead to blindness and so can eye diseases like, glaucoma. Vision loss from accidents and diseases is permanent since severed nerves rarely grow back. However, researchers at the University of Connecticut School of Medicine injected a small piece of a larger protein, called a peptide, into mice, allowing their severed optic nerves to regrow from the injury site to the optic chiasm within six weeks. To reach targets further in the brain, a longer trial of three months would be needed.
It is known that creating inflammation in the eye before nerve injury could induce some nerve cell growth. The trouble with this is that inducing eye inflammation in humans is not practical or desirable, and it’s impossible to predict traumatic injuries in advance.
Therefore, researchers focused on identifying what aspect of inflammation promotes nerve regeneration. One result of inflammation is that it brings in marcophages, immune cells that do many things, including secreting a protein called fibronectin. They found that this protein encourages optic nerve cells to regrow.
Still, in most cases of optic nerve injuries, nerve cells have limited exposure to fibronectin due to its low levels near the nerve. Also, doctor aren’t able inject fibronectin because it is too large of a protein. So, researchers found another way to get the protein into the eye.
They broke up fibronectin into small pieces called peptides, making them easier to inject. They then took the peptide that interacted with the optic nerve cells, synthesized it and injected it into the eyes of mice who had their optic nerves injured.
As a result of the injections, more nerve cells survived and many began to grow. Within six weeks the optic nerves had regenerated densely through the injury site, with many reaching the optic chiasm. The mice with the best results were ones that received gene therapy along with the peptide injections. Yet, the peptide injections alone were enough to produce strong growth in the nerve fibers.
Work in eye transplants and optic nerve regeneration will transform treatments for eye disease and injuries. In the case of THEA, these advances may also lead to breakthroughs in treating spinal cord injuries. Once again, research shows what is possible and what was once lost can be regained.
https://today.uconn.edu/2024/12/nerve-regrowth-in-sight/#