PITTSBURGH — Scientists have strived for successful eye transplants for centuries. Early attempts read like the diary of Mary Shelley: implanting a dog’s eye into a rat’s groin, transplanting a rat’s eye onto the neck of another rat, plucking the eye of a sheep from one socket and placing it into the other.

But never has a whole-eye transplant been successfully done in a living person. The eye’s complex web of muscles, blood vessels, and nerves — connected directly to the brain — has doomed past experiments to failure.

Now a team of Pittsburgh transplant surgeons aims to turn that tide, and they’re hopeful they can do so in just the next decade, using donor eyes to restore sight in people who have suffered traumatic eye injuries.

“I’m hopeful that in 10 years we will be doing eye transplants in humans,” said Dr. Kia Washington, plastic surgeon at University of Pittsburgh Medical Center and head of the research team. “There are people who are very skeptical, obviously, for obvious reasons. It is kind of a moonshot.”

And it’s a moonshot that’s of special interest to the Department of Defense, which is the main funder of the project. Traumatic eye injuries are the fourth most common combat wound for American soldiers. Counting both soldiers and civilians, nearly 1 million Americans are living with impaired vision due to eye injury. With donor eyes, Washington and her colleagues believe, many could one day see again.

Dr. Kia Washington in her lab at the University of Pittsburgh Medical Center.
Dr. Kia Washington in her lab at the University of Pittsburgh Medical Center.

Suturing sight

The first reported eye transplant attempts in animals began in the 19th century and peaked during World War II. As recently as 1977, a task force at the National Eye Institute concluded, after thoughtful laboratory investigation, that whole eye transplants could not be successful. These experiments were plagued with issues of immune rejection, inadequate blood flow, and lack of nerve function.

If the transplanted eye is ever to see, nerve connections are essential — and also the most complicated part of an eye transplant. The optic nerve, which connects the eye to the brain, is part of the central nervous system, along with the brain and spinal cord. While nerves elsewhere in the body — say, those in the fingers, or on the scalp — survive injury and regenerate easily, the central nervous system is not so resilient.

But Washington and team have begun to crack the code of the optic nerve, keeping its cells alive outside the body and coaxing it to regrow in a donor animal.

And recent decades have seen tremendous advances in other aspects of transplant medicine, including immunosuppressive drugs and microsurgical techniques, Washington said, which have allowed transplants that were previously impossible.

“Ten years, 20 years before hand transplantation occurred, there was a lot of skepticism and simply the technology wasn’t there,” Washington said. “You can argue the same thing with eye transplantation.”

The team took a major step forward last month with a paper showing the successful transplant of a rat’s eye into another rat, including joining the optic nerves. The organ was healthy and alive up to two years later. The next stage, with the DoD funding, is to regenerate the nerves to actually restore sight in rodents, primates, and, eventually, people.

“The development of the rat [eye and partial face transplant] model, by Kia, is a huge advancement in being able to conduct the complex science needed to successfully transplant a whole eye,” said Rob Nickells, a collaborator with Washington who is a professor of ophthalmology and visual sciences at University of Wisconsin. “I would confidently say that given success of the [nerve] questions, she will be the first surgeon to accomplish this feat.”

Dr Kia Washington's lab
An ERG machine is used to check nerve viability in transplanted rat eyes.

A question of nerve

The key to these eye transplants, team members say, is the problem of the delicate optic nerve. The first hurdle was simply keeping the nerve alive.

“Just harvesting an eye for transplant is telling all the [optic nerve] cells that they’ve gotta die,” Nickells said.

In tests on mice, Nickells zeroed in on the BAX gene, a key player that orchestrates cell death. In 2010, he discovered that mice without this gene didn’t lose any of their optic nerve cells after injury, even years later — whereas in a normal mouse all of the cells were dead within three weeks.

Since then, Nickells has been working on how gene expression — not just the mere presence of BAX or other genes — impacts neuron survival. In the future, he plans to begin searching for a drug candidate that could block BAX, which could theoretically be added to the solution that preserves the donor eye until it can be transferred to its recipient.

The second hurdle, after keeping the cells alive, is actually spurring the nerve to grow. The donor nerve can’t simply join together with the recipient stump, but instead has to regrow all the way from the eye to the brain. In an adult, nerve cells lack this ability for growth, but Harvard Medical School professor of neurology Zhigang He has been working with Washington to try to turn back the clock.

“We need to find a way to reprogram old neurons to be young neurons,” He said. “Adult neurons don’t have growth ability. Somehow we have to make them able to regrow.”

In January, He and his team published a paper showing that a novel drug cocktail can do exactly that in mice. The drug disables a tumor suppression pathway and allows neurons to grow. When researchers cut the optic tract just outside the brain, the nerve regrew to bridge the gap within 28 days.

But could the mice actually see? To answer this question, eight weeks after injury the researchers showed the mice a rotating drum painted with vertical black and white stripes. A normal mouse naturally turns its head to follow the stripes. The mice with regenerated nerves didn’t budge, indicating that they couldn’t see.

He realized that this failure to restore sight happened because the freshly grown nerves differed in a key way from normal nerves: They lacked insulation, so electrical signals from the eye diminished before reaching the brain.

This, He knew, is the exact same problem as is seen in the nerves of people with multiple sclerosis. So the researchers gave these same mice the MS drug 4-AP, and three hours later tested them again. Suddenly the animals started moving their heads in response to the rotating drum. Blind mice could once again see.

Dr Kia Washington
Washington and Dr. Chiaki Komatsu inspect a rat’s eye in their lab.

Seeing the future

Accomplishing a similar feat in humans could be possible within 10 years, said Stanford associate professor of neurobiology and ophthalmology Andrew Huberman, who is not involved with Washington’s research. But he says that it’s a route that makes less sense than using newer additions to the biomedical toolkit.

“I don’t think we’re just going to take an eye from a recently deceased person and put it on someone else … and that person’s going to see,” Huberman said. “I think it’s going to be a combination of biologics and engineering” — like, for instance, combining a donor eye with neural stem cells.

If scientists were able to grow a new retina on the donor eye from stem cells, Huberman said, those fresh retinal neurons might more easily grow projections that can stretch all the way to the brain.

Regardless of the approach, many challenges lie ahead. Nickells has been working with mice whose optic nerves were crushed, so it remains to be seen whether the same principles will work when the nerve is cut. And He’s team has been able to regrow the rodent optic nerve at most 1 centimeter; by comparison, the distance from the eye to the brain in a human is a chasm.

For Washington, the next steps involve finding noninvasive ways to monitor possible rejection of the donor eye in both rats and primates. This will prevent her from having to biopsy the eye to look for rejection, which is the standard way to monitor other kinds of transplants. Once she identifies rejection, she wants to see how the eye responds to the standard immunosuppressive drugs.

The first human recipients of whole eye transplants, Washington predicts, will be those already slated for a face transplant. Many of these patients are blind and will have to take immunosuppressive drugs regardless, so the risk versus reward ratio of transplanting the eye is very low.

And despite the hurdles ahead, Washington believes transplantation is the best way forward in treating vision loss from eye injury. “Particularly in the traumatic setting, it’s really about being able to restore form and function combined in one procedure.”

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  • Very positive, encouraging and wonderful efforts on the part of all -keep it up!!!!

    Am following all articles and developments for regenerating optic nerves, as my beloved still cannot see, in one eye, after 10 operations..
    He was 16 years an emergency doctor in Lausanne University.
    And active as he is, a tremendous blow for him.
    So, be so kind as to froward me all and any reports on reactivating growth in optic nerves and or neural stemcells treatments.
    Am very much in favour of stemcells therapies cos i have had a few done to my face, hair and it works wonders at rejuvenation.
    So i really believe in it‘s healing possibilities.
    As they are also routinely used to generate soft tissues for gums and healing wounds pre dental implants too. Professor Ottaviano Tapparo (Natrail Klinik, München) Münich is a leading pioneer in stemcells applications.

    With many thanks in advance,
    Yours sincerely,
    Lian
    +49 174 398 7723 (whatsapp)

  • Your article and information was very informative and encouraging I have glaucoma and have had the trab in both eyes, and my optic nerve is damage. Where are medical break- throughs for correcting and regeneration of the damage nerve to restore sight? Thankful. I do have sight in both eyes and able to drive during the day. Just want to know what progress has been made.

  • I lost 80% of my sight 10 years ago. I had a steel drill bit go though the center of my eye. They rebuilt the eye replaced the center leans (woung) perception. Pulled the iris back in place. The found a donor for my cornea and replaced it. But the rod bumped my optic nerve. My sight is low, only 20% and there are 3 black dot in my field of vision. Do to the fact that the rode only bumped my optic nerve and not the brain. I believe ( you can replace the eye, so I will be functional. Please call me 520-353-5082 Hoping to hear from you soon

  • My husband, sheldon, had ratialkeratonomy surgery in one eye and a few weeks later had it in the other eye in the 1990’s. He had a lot of problems with the right eye and a few years ago had a cornea transplant in the right eye, which took approximately 20 stiches. Now he ‘s told he has beginning AMD. Is there any hope of clearer vision? He is 78 years old.

  • My son received pillet injury in his left eye, and expecting danger to his optic nerve, would be know fate of optic nerve after removal of stuccked pillet , what can I do ?

  • My nephew, a 32 year old Army Capt, was a victim of the ISIS suicide bombing in Syria last month. He lost one eye & too much damage 2 optic nerve in second. He also needs several reconstructive surgeries on his face, thus wondering about the statement above that first recipient may be someone in need of a face transplant. Wondering if the research for humans still makes the eye transplant impossible. He is in Walter Reed at the moment & we’re just devastated by the destruction done by the bomb. If only he could see out if the one eye, at least. Not sure if optic nerve was completely severed. How much different is a rat’s eye than a humans?

  • My child lost both eyes due to retinoblastoma so both eyes were enuculated. Can he be a possible candidate for the eye transpalnt in future?

    • Hi Elizabeth
      They are conducting research and our hopes are that in the future we will be able to do human eye transplants successfully. At the moment it cannot be done on humans but it has been tried out on animals following some success stories. I am also waiting for the day a human eye can be successfully translated as my kid also needs one. Be strong and keep the faith

  • My baby Gungun who is two and half year old suffered from ratinablastoma .I want to know about whole eye transplant.

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