researchers at Weill Cornell Medical College have deciphered a mouse’s
retina’s neural code and coupled this information to a novel prosthetic
device to restore sight to blind mice. The researchers say they have
also cracked the code for a monkey retina—which is essentially identical
to that of a human—and hope to quickly design and test a device that
blind humans can use.
breakthrough, reported in the Proceedings of the National Academy of
Sciences (PNAS), signals a remarkable advance in longstanding efforts to
restore vision. Current prosthetics provide blind users with spots and
edges of light to help them navigate. This novel device provides the
code to restore normal vision. The code is so accurate that it can allow
facial features to be discerned and allow animals to track moving
lead researcher, Dr. Sheila Nirenberg, a computational neuroscientist
at Weill Cornell, envisions a day when the blind can choose to wear a
visor, similar to the one used on the television show Star Trek. The
visor’s camera will take in light and use a computer chip to turn it
into a code that the brain can translate into an image.
an exciting time. We can make blind mouse retinas see, and we’re moving
as fast as we can to do the same in humans,” says Dr. Nirenberg, a
professor in the Department of Physiology and Biophysics and in the
Institute for Computational Biomedicine at Weill Cornell. The study’s
co-author is Dr. Chethan Pandarinath, who was a graduate student with
Dr. Nirenberg and is currently a postdoctoral researcher at Stanford
new approach provides hope for the 25 million people worldwide who
suffer from blindness due to diseases of the retina. Because drug
therapies help only a small fraction of this population, prosthetic
devices are their best option for future sight.
is the first prosthetic that has the potential to provide normal or
near-normal vision because it incorporates the code,” Dr. Nirenberg
Discovering the code
vision occurs when light falls on photoreceptors in the surface of the
retina. The retinal circuitry then processes the signals from the
photoreceptors and converts them into a code of neural impulses. These
impulses are then sent up to the brain by the retina’s output cells,
called ganglion cells. The brain understands this code of neural pulses
and can translate it into meaningful images.
is often caused by diseases of the retina that kill the photoreceptors
and destroy the associated circuitry, but typically, in these diseases,
the retina’s output cells are spared.
prosthetics generally work by driving these surviving cells. Electrodes
are implanted into a blind patient’s eye, and they stimulate the
ganglion cells with current. But this only produces rough visual fields.
groups are working to improve performance by placing more stimulators
into the patient’s eye. The hope is that with more stimulators, more
ganglion cells in the damaged tissue will be activated, and image
quality will improve.
research teams are testing use of light-sensitive proteins as an
alternate way to stimulate the cells. These proteins are introduced into
the retina by gene therapy. Once in the eye, they can target many
ganglion cells at once.
Dr. Nirenberg points out that there’s another critical factor. “Not
only is it necessary to stimulate large numbers of cells, but they also
have to be stimulated with the right code — the code the retina normally
uses to communicate with the brain.”
This is what the authors discovered—and what they incorporated into a novel prosthetic system.
Nirenberg reasoned that any pattern of light falling on to the retina
had to be converted into a general code—a set of equations—that turns
light patterns into patterns of electrical pulses. “People have been
trying to find the code that does this for simple stimuli, but we knew
it had to be generalizable, so that it could work for anything—faces,
landscapes, anything that a person sees,” Dr. Nirenberg says.
Vision=chip plus gene therapy
a eureka moment, while working on the code for a different reason, Dr.
Nirenberg realized that what she was doing could be directly applied to a
prosthetic. She and her student, Dr. Pandarinath, immediately went to
work on it. They implemented the mathematical equations on a “chip” and
combined it with a mini-projector. The chip, which she calls the
“encoder” converts images that come into the eye into streams of
electrical impulses, and the mini-projector then converts the electrical
impulses into light impulses. These light pulses then drive the
light-sensitive proteins, which have been put in the ganglion cells, to
send the code on up to the brain.
entire approach was tested on the mouse. The researchers built two
prosthetic systems—one with the code and one without. “Incorporating the
code had a dramatic impact,” Dr. Nirenberg says. “It jumped the
system’s performance up to near-normal levels—that is, there was enough
information in the system’s output to reconstruct images of faces,
animals—basically anything we attempted.”
a rigorous series of experiments, the researchers found that the
patterns produced by the blind retinas in mice closely matched those
produced by normal mouse retinas.
reason this system works is two-fold,” Dr. Nirenberg says. “The
encoder—the set of equations—is able to mimic retinal transformations
for a broad range of stimuli, including natural scenes, and thus produce
normal patterns of electrical pulses, and the stimulator (the light
sensitive protein) is able to send those pulses on up to the brain.”
these findings show is that the critical ingredients for building a
highly-effective retinal prosthetic—the retina’s code and a high
resolution stimulating method—are now, to a large extent, in place,”
reports Dr. Nirenberg.
Nirenberg says her retinal prosthetic will need to undergo human
clinical trials, especially to test safety of the gene therapy
component, which delivers the light–sensitive protein. But she
anticipates it will be safe since similar gene therapy vectors have been
successfully tested for other retinal diseases.
“This has all been thrilling,” Dr. Nirenberg says. “I can’t wait to get started on bringing this approach to patients.”
study was funded by grants from the National Institutes of Health and
Cornell University’s Institute for Computational Biomedicine.
Both Drs. Nirenberg and Pandarinath have a patent application for the prosthetic system filed through Cornell University.
Source: New York- Presbyterian Hospital/Columbia University Medical Center