science: The quest to turn eye transplants from science fiction into reality

When an eye is lost, darkness reigns. And those
who treat eye trauma and disease are, in a sense,
groping in the dark themselves. They have little to
offer the young girl who tripped while trick-or-
treating one Halloween night, cracking her skull
and severing the optic nerve, or the 60-year-old
who sees only light and shadows, because
glaucoma has destroyed cells in that same
conduit. Vijay Gorantla, a plastic and
reconstructive surgeon at the University of
Pittsburgh Medical Center, along with
collaborators there and at nine other centers,
want to turn eye transplants from science fiction
into reality. They have their work cut out for
them. The most daunting challenge is coaxing
nerves to regenerate and connect the donor eye
to the recipient's, and there are a host of other
hurdles, too. But those holding the purse strings
are ready to gamble, and researchers hope early
models in pigs and rats will serve as a guide.
In his first-floor lab at the University of
Pittsburgh Medical Center (UPMC) in
Pennsylvania, Vijay Gorantla is hunched over a
blind pig. Under the glare of an operating
room light, he's venturing into a shadowy
landscape.
Gorantla's terrain is an elegant, tightly
controlled 7.5-gram bundle of cells: the eye.
Pigs and humans share similar ocular
anatomy, and Gorantla, a plastic and
reconstructive surgeon, has sliced this
animal's optic nerve in two. Now the question
is, can he help it see again?
When an eye is lost, darkness reigns. And
those who treat eye trauma and disease are,
in a sense, groping in the dark themselves.
They have little to offer the young girl who
tripped while trick-or-treating one Halloween
night, cracking her skull and severing the
optic nerve, or the 60-year-old who sees only
light and shadows, because glaucoma has
destroyed cells in that same conduit.
Physicians have transplanted hearts and
lungs, faces and hands, a uterus, the
abdominal wall. Now, Gorantla wants the eye
on that list. He and his colleagues have their
work cut out for them. The most daunting
challenge is coaxing nerves to regenerate and
connect the donor eye to the recipient's brain.
But they must also establish blood flow to a
transplanted eye; control how the immune
system responds to it; and preserve the
intricate mechanisms that keep the eye moist,
blinking, and able to focus. No one has
achieved success even in an animal, and
Gorantla is starting from humble beginnings:
removing a pig's eye and reattaching it.
Those holding the purse strings are ready to
gamble. Last fall, the Department of Defense
(DOD) awarded $1.25 million over 2 years to
three centers, including Gorantla's, to develop
animal models for whole-eye transplantation.
In 2013, the National Eye Institute (NEI) in
Bethesda, Maryland, announced the winner of
its “audacious goal initiative,” a reachable but
ambitious target for eye research. The choice
—“regenerate neurons and neural connections
in the eye and visual system”—encompasses
eye transplants, though isn't limited to them,
says Paul Sieving, director of NEI. “Science
fiction becomes reality eventually, doesn't it?”
Or, as Gorantla puts it, “if you don't think
about something being a possibility, nothing
can happen.”
GORANTLA HAS HELD TIGHT to that motto
since at least 1998, when he flew from
Manchester, U.K., to Louisville, Kentucky.
Fresh from surgical training in England, he
was en route to one of the world's premier
hand surgery programs. In the Manchester
airport before his departure, Gorantla grabbed
a copy of Time —and was startled to learn
that his new home was gearing up for what
would be the world's first successful hand
transplant. The 15-hour surgery took place 6
months later, in January 1999, on a 37-year-
old who had lost his hand in a fireworks
accident.
Hand transplants were very different from the
organ transplants that preceded them. “With a
solid organ, the minute you transplant it” and
reconnect the blood vessels, “it starts
functioning,” Gorantla explains. “All it needs is
a blood supply.” Hands include nerves, skin,
bones, and bone marrow. Each of these needs
to work for a transplant to succeed. Peripheral
nerves connecting the new hand to the rest of
the body have to regenerate—which they do,
albeit just 1 millimeter a day. In Louisville,
Gorantla assisted in two hand transplant
surgeries and followed the patients for years
afterward. “It was a process of self-education
and discovery,” he remembers. “I was right
there in front of the patient every day,
understanding how rejection happens …
understanding how patients adapt.”
In 2006, he relocated to UPMC to establish a
hand transplant program there. Face
transplants were just beginning, and Gorantla
wondered whether he might take them on.
The candidates he met were often Iraq War
veterans, their faces blown away.
Although Gorantla could offer these veterans a
new face, many had lost their eyes as well,
and he couldn't restore their sight. For them,
as for other blind people, the preferred
strategy for navigating the world is a Seeing
Eye dog. “We've outsourced it,” says Andrew
Huberman, a neuroscientist at the University
of California, San Diego (UCSD). “That's the
best thing we've got.”
So rather than dive into face transplants,
Gorantla focused on vision. About 5 years
ago, he began broaching the subject of eye
transplants with ophthalmologists. “I thought,
‘It's crazy,’” remembers Joel Schuman,
director of the eye center at UPMC. “The
barriers to success are very high.” The
greatest: Parts of the eye belong to the
central nervous system, and unlike peripheral
nerves in the hands and face, the central
nervous system was thought incapable of
repairing itself. Gorantla was eager to defy
dogma. “People said I was too disruptive;
they distanced themselves from me,” he
recalls.
He turned to history. Digging into medical
archives, Gorantla uncovered illustrations and
handwritten notes from 1885, when a Parisian
ophthalmologist had transplanted a rabbit's
eye into a young girl. Other efforts followed.
All failed miserably, of course—“the rabbit eye
was rejected immediately,” Gorantla says. But
still, the early attempts “really gave me
confidence to get back on track. … I was not
being completely stupid” to consider this.
MORE THAN A MILLION retinal ganglion cells
form a layer in the retina of the human eye.
Running from each is a nerve fiber called an
axon that stretches back into the brain.
Together, these fibers assemble into the optic
nerve, “a cable of 1 million phone wires,” as
NEI's Sieving describes it.
In Nature in 2011, Harvard University
neuroscientist Zhigang He and his colleagues
described crushing the optic nerve of mice
and deleting two genes in their retinal
ganglion cells. Losing those two genes helped
neurons sense stress and proliferate, and,
remarkably, they activated a host of others
that prompted at least 10% of the nerves to
regenerate. The work was replicated by other
labs, confirming that “it's possible to get
mouse axons to regenerate long distance,”
says Ben Barres, a neuroscientist at Stanford
University in Palo Alto, California, who wasn't
directly involved.
But did the newly sprouted nerve fibers travel
to the right place? In 2012, Harvard
neuroscientist Larry Benowitz, working
independently, supplied early evidence that
they did, at least partially: The axons reached
into visual centers of the brain. Preliminary
data hinted that the pupils of the mice
responded to light, suggesting they had
regained some vision, albeit a minuscule
amount. In a different Harvard lab, He is
studying how the regenerated nerves function,
performing electrophysiology on the cells and
behavior studies on his animals