Can a computer chip fill in for the eye's lost cells?
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Fishman and his interdisciplinary
team are growing nerve cells on a silicon chip to create an artificial
retina. Their goal: connect a camera to the cells, which would send
visual information to the brain. The chip would restore vision to
people with macular degeneration — which affects one in four
Americans over age 65. (larger
image available) |
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Let there be light
By Kendall Morgan
Photographs Leslie Williamson
Illustration Ian Worpole
Everyone knows you can’t believe everything you hear. But a growing
number of people can’t believe everything they see. Straight lines
can turn to squiggles, numbers and letters blink in and out and colors
fade to shades of gray. People with the most common cause of blindness — age-related
macular degeneration — find that a curtain is gradually drawn across
the world.
Luckily, Harvey Fishman, MD, PhD, senior research scientist in ophthalmology,
is a visionary. He's a pioneer with his sights set high, and his goal
is to rebuild the eye.
Macular degeneration affects one in four Americans over the age of 65,
with 130,000 new cases diagnosed each year. As the population ages, the
number will continue to rise. As is the case with heart disease, the
causes of AMD are likely to be many — the end product of a lifetime
of insults to the eye, says Fishman. Today, there are treatments to delay
the progression of the disease, but there is no cure.
Fishman, with the help of co-investigator Mark Blumenkranz, MD, professor
of ophthalmology, and a diverse team of experts, has set out to attack
blindness at its core. The answer, he says, is a silicon vision chip
with a command of the language of sight. "This is the wild, wild west
of vision research," says Fishman. He and his team will cover a lot of
ground before reaching their final destination, but already the future
looks brighter.
The early stages of macular degeneration include a wasting away of part
of the eye's machinery, a protective cell layer called the pigment epithelium
that coats the back of the eye. If clinicians catch the disease early
enough, they can restore the lost tissue layer and successfully treat
the disease. But without this barrier, cells of the retina — the
eye's microprocessor — are gradually lost.
The retina's job is to receive light signals and transmit messages out
to ganglion cells and on to the brain. Its role is so sophisticated some
consider the retina a miniature brain in itself. In essence, an eye without
a retina is like a camera without film, Fishman says. Images can’t
be captured.
"The disease knocks out one circuit," Fishman says. "But the rest of
the cells are still there, ready to function. We have an opportunity
to tap into the eye and replace the lost film."
Fishman isn’t the first to attempt this. The idea dates back to
1956 when a light-sensitive selenium cell placed behind the retina was
shown to restore the perception of light in blind patients, however briefly.
Since then, groups have sought to access the brain's visual system via
a variety of routes: through electrodes ending in the brain or by way
of a cuff surrounding the optic nerve — the information superhighway
from the eye to the brain.
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This 1/2-cm-wide chip is stamped
with patterns made of growth factors. Its purpose: to test how
well the chemicals steer nerve cell growth.
The Makings for Eye Drama
Experts from Engineering and Medicine Join together against
Blindness
What do you get when you cross an
ophthalmologist with a chemical engineer and an expert in retinal
surgery? Real hope for sight restored.
When Harvey Fishman, MD, PhD, a senior research
scientist in the Department of Ophthalmology, nailed down his
plan for a new and improved vision chip, he looked no further
than across the street to round up the experts who could make
the dream come true. In fact, he got the seed of the idea while
eating lunch with Stacey Bent, PhD, an assistant professor of
chemical engineering at Stanford and a friend of Fishman's from
their days as graduate students.
"Harvey has the big picture of what he wants
to make happen in the eye, " says Bent." I help figure out how
to make it a reality."
It's not every day that chemical engineers
have the opportunity to oversee surgery and get immediate, firsthand
experience with problems in the design of their materials. But
it's that kind of interaction that makes this project a winner,
Fishman says.
Indeed, the research
has progressed at an incredibly rapid pace, a synergistic effect
of the many great minds behind it. "It's been very stimulating," says retinal surgeon
Mark Blumenkranz, MD, professor and chair of ophthalmology. "Everyone
is working toward a common goal to restore vision. It couldn't
be accomplished by one group alone."
Fishman predicts
more and more collaboration in the future of scientific research. "We're moving toward great
advancements made at the crossroads of diverse disciplines," Fishman
says "one chip at a time."
Kendall Morgan
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A Chip Can Do the Trick
In the early 1990s, researchers began exploring the current method of
choice: a prosthetic vision chip implanted into the retina. Vision chip
teams are scattered around the world in the United States, Germany and
Japan. Still, success has been elusive. Temporary chips have produced
the sensation of light in blind patients, but nothing close to useful
vision.
Fishman is a relative newcomer to the field of prosthetic retinas and
he's full of fresh ideas. His team is working from many different angles
to attack problems at every level, from the fabrication of the chip to
the practical details of surgery.
The eye responds to light, but also to contrast between light and dark,
requiring some cells to be stimulated while others are inhibited. Existing
vision chips fall short because they don’t preserve information
about contrast, Fishman realized.
"The retina is arranged very precisely," explains Michael Marmor, MD,
ophthalmology professor and a project collaborator. "If you just plop
a chip down in the middle, you aren’t sending information to the
brain in any rational way."
Ultimately, the goal is a chip that would fill in for lost photoreceptors,
relaying signals to the brain in a language it can understand. The challenge,
then, is to connect single cells in the eye to individual pixels of a
digital video camera and to get the chip talking to the eye's intact
cells. To accomplish this, the researchers have learned to train nerve
cell growth.
First, they make a stamp, "like a child's rubber stamp but in exquisite
detail," describes Stacey Bent, PhD, assistant professor of chemical
engineering. Rather than stamping in ink, they stamp out a pattern in
chemical nerve growth factors. As soon as a growing nerve hits the stamped
trail, it sticks to it like glue, growing along in a zigzag or other
pattern. It's a trick that makes it possible to grow nerves to the exact
locations of pixels on a chip, Bent says.
While other vision chips attempt communication with the healthy cells
of the eye via electricity, Fishman hopes to create a chip that can speak
the more exact language of chemistry. "Different chemicals tell cells
different things," Marmor explains. "If you just shock the retina you
can get a sense of light, but with a neurotransmitter you may get a more
specific message."
Design and Conquer
The team's research has progressed at an explosive rate. At the May
2002 meeting of the Association for Research in Vision and Ophthalmology,
Fishman showed how neurotransmitters and growth factors can stimulate
and direct nerve-cell growth on a chip. Now they’ve moved on to
questions of chip design and surgery. "If you had told me a year ago
that we’d have gotten as far as we have, I would have laughed," Fishman
says. Yet plenty of hurdles remain.
"It's promising, but it's a totally open question whether it will work," says
David Eagleman, PhD, a neurobiologist at the Salk Institute in La Jolla,
Calif. The retinal code hasn’t been completely cracked, so it's
unclear whether chips will send the right kind of signal, he says. However,
he adds, the brain is amazingly flexible and may be able to adapt to
new kinds of visual inputs.
Even if the Stanford chip isn’t the answer to every question in
electronic vision, Fishman predicts the technology developed along the
way will seep into other important medical arenas from drug delivery
to the treatment of spinal-cord injuries. "By combining the best in microtechnology
with the best in cell biology," Fishman says, "we will advance on new
treatments."
Comments? Contact Stanford Medicine at
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