Bascom Palmer’s whole-eye transplant will connect the brain and the optic nerve to restore sight
By Josh Baxt
Illustration by hitandrun
orldwide, around 43 million people are blind, and many more are visually impaired. Unfortunately, for many who have lost their sight, medical science has few answers. They may learn braille, lean on their other senses or even use echolocation, but actual sight is lost to them.
That may be changing. The Miller School is part of a multi-institutional effort, begun in 2005, to develop whole-eye transplants, which could help those who have lost their sight through accidents, glaucoma, diabetic retinopathy and other causes.
To get there, the Bascom Palmer Eye Institute is orchestrating a whole-eye transplant “moonshot.” It’s an all-hands-on-deck project, with contributions from ophthalmologists, surgeons, engineers, neuroscientists and many others. In all, 17 Miller School faculty members from nine different departments are participating. There are four intricate challenges to be addressed, and it’s going to take the entire team to get them done.
The search for a solution to the first challenge is being co-led by scientist Daniel Pelaez, M.S. ’07, Ph.D. ’11, and surgeon David Tse, M.D. ’76. “We are developing a new technique to recover a donor eye,” explained Dr. Tse, who is professor of ophthalmology, the Dr. Nasser Ibrahim Al-Rashid Chair in Ophthalmology and founder of the Dr. Nasser Ibrahim Al-Rashid Orbital Vision Research Center at Bascom Palmer. “We must recover the eye, preserve it for 48 hours and ensure its viability for transplant.”
Recovering the donor eye will be challenging, but it may be the easiest step in this protocol. Dr. Tse and others have already established the surgical techniques required to remove an eye without damaging it. However, once the eye is removed from the body, the process gets quite complex.
The eye needs constant blood flow to supply oxygen and nutrients and will not survive long without it. Inside the body, this is not usually an issue, but donor eyes will spend significant time on their own. Dr. Tse and Ashutosh Agarwal, Ph.D., associate professor of engineering, are developing a miniature extracorporeal membrane oxygenation (ECMO) machine. ECMOs are generally used to supplement heart and lung function for cardiovascular patients, but heart units weigh around 100 pounds. They are designing this much-smaller ECMO for eyes to weigh only 25 pounds and be the size of a carry-on bag.
The eye-ECMO will provide oxygenated blood for the donor eye, but that’s only part of its role. Once the optic nerve is severed, the body naturally generates inflammatory molecules to address the injury. Unfortunately, these proteins can cause further damage to a donor eye, complicating the reattachment process when it is transplanted. The eye-ECMO will also infuse the eye with anti-inflammatory molecules, helping protect it. In addition, the instrument will continuously monitor the eye’s health and suitability for transplant.
“The machine will assess the eye’s response to being outside the body, including its pH, glucose, potassium and other levels,” Dr. Tse said. “This real-time readout provides invaluable data to react and give the eye what it may need. It’s much like the glucose monitoring systems diabetic patients use to learn if they need more insulin.”
In addition to the eye-ECMO, the team is inventing new ways to assess transplant eyes, using cameras, lights, electrophysiological instruments and other means to check blood flow, electrical responses and retinal function.
“At Bascom Palmer, we are quite good at testing eye function when it’s inside the head, but not when it’s outside the human body,” said Dr. Pelaez, scientific director of the Dr. Nasser Al-Rashid Vision Research Center and research associate professor of ophthalmology. “We have to build an entire technology suite to test these functions in an excised eye.”
David Tse, M.D.
“We must recover the eye, preserve it for 48 hours and ensure its viability for transplant.”
From Disease-Centered to Patient-Centered Care
Daniel Pelaez, M.S., Ph.D.
“Many nonmammals are capable of regenerating the optic nerve, so we’ve been studying these mechanisms.”
The greatest barrier to successful whole-eye transplants is connecting the optic nerve to the eye. Surgically reattaching it will not be enough — there needs to be a way to regenerate the connection to complete the circuit.
Dr. Pelaez and colleagues have spent years identifying the biological mechanisms that help regenerate optic nerves. He didn’t have to look far for clues: many lower vertebrates have natural regenerative capacity. Tadpoles, for example, regenerate their optic nerves, and are particularly good models because they’re small and transparent.
Over many years, Pelaez and his team have been making slow but steady progress toward identifying molecules that could support regeneration in people. A recent study showed they could regrow optic nerves in rats, fellow mammals that, normally, have minimal regenerative capacity.
“Many non-mammals are capable of regenerating the optic nerve, so we’ve been studying those mechanisms,” Dr. Pelaez said. “We’ve also been looking at molecules that can initiate regeneration in higher mammals. By converging these two lines of investigation, we found a sweet spot: an overlapping mechanism we believe increases regeneration in the central nervous system.”
As these regenerative technologies evolve, they could have much wider applications, eventually repairing spinal cord or traumatic brain injuries. These techniques could also help fix damaged optic nerves, which are not uncommon.
“In clinical practice, we never see an optic nerve actually cut in half, outside of an eye transplant,” Dr. Tse said. “However, we frequently see traumatic optic nerve injuries from car accidents or people getting hit in the eye. The wires are still connected, they’re just not functioning properly. Regenerative medicine could do a lot to help these people.”
The whole-eye transplant research team is close enough to their ultimate goal that they have started to look at rehabilitating the transplanted eye. Once again, this has never been done before, and they are relying on decades of discovery research to develop the most effective rehabilitation techniques for teaching the central nervous system to see again.
“The first step is actually solving the problems associated with whole-eye transplants, and we are pretty far along,” Dr. Pelaez said. “We have also assembled a group to develop the rehabilitation protocols, and they will be working with everyone else on the moonshot team to make this process as seamless as possible for patients.” 
