[Nfbf-l] {Spam?} Repairing or Replacing the Optic Nerve: New Frontiers in Vision Technology Research

[Alan Dicey]

    Dear Friends,
Some one just sent this to me, but apparently more articles regarding 
restoring vision can be found on the AccessWorld  Web Site.
Main article starts next
Repairing or Replacing the Optic Nerve: New Frontiers in Vision Technology 
Research
Bill Holton

http://www.afb.org/afbpress/pub.asp?DocID=aw170307
In the September 2013 issue of AccessWorld , we described four 
groundbreaking advances in low vision enhancement, including the Implantable 
Miniature Telescope from VisionCare Ophthalmic Technologies, and the Argus 
II Retinal Prosthesis from Second Sight. The first of these is a pea-size 
telescopic lens that increases the useable vision of individuals who have 
lost central vision due to end-stage age-related onset macular degeneration. 
The Argus II is aimed toward people with late-stage retinitis pigmentosa 
(RP). The Argus II uses a wireless signal to stimulate the optic nerve 
directly via an implanted array of electrodes, bypassing the rods and cones 
damaged by RP.
As remarkable as these solutions may be, they do have one stumbling block in 
common: they each assume the recipient possesses a functioning optic nerve 
that can adequately transmit visual signals to the brain for processing. But 
what if the optic nerve has been damaged by glaucoma, multiple sclerosis, or 
trauma? Might there be some way to mend these most complex and fragile of 
nerve fibers? Or even better, bypass them altogether?
In this article we will describe two recent research breakthroughs--one that 
shows the potential to help regenerate damaged optic nerves, and the second, 
a system called Gennaris, that may produce vision without the optic nerve, 
or even the eye itself.
Regenerating an Optic Nerve
The optic nerve is one of the most important nerves in the body, second only 
to the spinal cord (the spinal cord includes thousands of nerve strands 
while the optic nerve has but one). So fifteen years ago when Zhigang He, 
Professor of neurology at the Boston Children's Hospital F.M. Kirby 
Neurobiology Center set up a lab to investigate ways to regenerate nerve 
fibers in people with spinal cord injuries, he decided the best place to 
start would be to attempt neural regeneration in damaged optic nerves as a 
proxy.
Others have tried optic nerve regeneration or repair. The first attempts 
spliced bits of the sciatic nerve to replace damaged optic nerve. Most axons 
didn't regrow. About eight years ago, Dr. He's group tried gene excision to 
delete or block tumor-suppressing genes. This prompted some optic nerve 
regeneration, but it also increased cancer risks. Their recent work with Dr. 
Joshua Sanes at Harvard found a gene therapy strategy to enhance growth 
factor activities, which could mimic the regeneration effects induced by 
tumor suppressor deletion. Nevertheless, the number of regenerated axons by 
these approaches was limited.
He and his co-senior-researcher, Boston Children's Hospital Assistant 
Professor of neurology Michela Fagiolini, took gene therapy a step further. 
They used a gene therapy virus called AAV to deliver three factors to boost 
growth factor responses into the retina, which is part of the optic nerve 
system.
"Over time we were able to regenerate increasingly longer nerve fibers in 
mice with damaged optic nerves," he reports. "Unfortunately, the new neural 
fibers did not transmit impulses, known as action potentials, all the way 
from the eye to the brain, so there was no new vision."
He and Fagiolini traced the problem to the fact that the new nerve fibers 
were growing without the fatty sheath called Myelin. Myelin insulates nerve 
fibers and keeps neural signals on track, much as the insulation surrounding 
a copper wire directs electrical current to the lamp instead of into the 
wall studs and outlets.
Turning to the medical literature, he and Fagiolini read about a potassium 
channel blocker called 4-aminopyridine (4-AP) which is known to improve 
message conduction in nerve fibers that lack sufficient Myelin. Indeed, 4-AP 
is marketed as AMPYRA to treat MS-related walking difficulties, which also 
involve a loss of myelin.
"When we administered 4-TP the signals were able to go the distance," says 
Fagiolini. A separate lab, where they did not know which of the blind mice 
had been treated, confirmed that the treated mice responded to moving bars 
of light while the control group did not.
"There is still considerable work to be done before this treatment is ready 
for human trials," He says. For example, the team used a gene therapy virus 
to deliver the growth factors that stimulated optic nerve regeneration, but 
He and Fagiolini believe they can produce an injectable "cocktail" of growth 
factor proteins that could be equally effective. "We're trying to better 
understand the mechanisms and how often the proteins would have to be 
injected," says He.
Also yet to be solved are the potential side effects of using 4-AP to 
increase optic nerve signal transmission. The medication can cause seizures 
if given chronically, so He and Fagiolini have begun testing non-FDA 
approved 4-AP derivatives which would be safer for long-term use. Despite 
the remaining hurdles, He and Fagiolini remain optimistic. "At least now we 
have a paradigm we can use to move forward," He says.
The Mind's Eye
Regenerating the optic nerve could help millions, but what if we could 
bypass the optic nerve altogether and see without one, or even without 
physical eyes? That's the goal of Arthur Lowery, Professor of electrical and 
computer systems engineering at Australia's Monash University. Lowery and 
his team are currently working on Gennaris, a system that will stimulate the 
brain's visual cortex directly, sending a grid of electrical impulses that 
the brain can interpret as recognizable patterns of light and dark.
Research into "brain" vision goes back to the 1960s. "At that time you 
needed a room full of equipment to get any results at all," observes Lowery. 
"Even as little as ten or fifteen years ago, producing a grid of three 
hundred points of light meant passing a bundle of 300 separate wires from 
the brain to a large, external video camera." Lowery and his team are 
building on this previous work, taking advantage of the considerable 
progress which has been made over the past decade in processing power, 
component miniaturization, wireless data transmission, and induction power 
transmission such as that now found on some cell phones which can be placed 
atop the charger instead of needing to be plugged in.
In normal vision, light passes through the eye's pupil and lens and 
stimulates rods and cones, which are the photo-receptive cells covering the 
retina. These photochemical signals are transformed into neural impulses, 
which in turn are transmitted along the optic nerve to the visual cortex. 
There, the brain turns these impulses into recognizable shapes and images, 
otherwise known as vision.
As it happens, the neurons in the visual cortex can also be stimulated by 
contact with tiny electrodes. "We know from previous research that we can 
produce flashes of light that appear in roughly the same spot whenever that 
same region of the visual cortex is stimulated," states Lowery. "If we can 
create a number of these flashes more or less simultaneously, we can create 
a rudimentary grid of light and dark the brain could interpret as an image." 
Imagine a square of sixteen light bulbs creating the letter O by switching 
on the twelve perimeter bulbs and leaving the four center lights turned off. 
Or a letter L created by braille dots 1, 2, and 3, with the rest of the cell 
left blank.
The Gennaris team hopes to create just such a grid using tiny ceramic tiles 
embedded directly onto a test subject's visual cortex. "Each tile is 
approximately 9 millimeters square--about a third of an inch--with 
forty-three working electrodes on each tile," Lowery explains. "These 
electrodes will penetrate 1.5 to 2 millimeters into the visual cortex, 
reaching what is known as Layer Four, the brain region most directly 
stimulated by the optic nerve."
A small video camera will transmit real-time imagery to a pocket-size 
processing unit. There, special algorithms will determine the most essential 
aspects of each image and break them down into a running series of grids of 
light and dark. The grids will be streamed wirelessly to a magnetic 
induction coil placed against the back of the patient's head nearest the 
visual cortex. The induction coil will be able to remotely spawn a tiny 
charge in each of the electrodes as appropriate, which will then stimulate 
the visual cortex much the same way as the optic nerve would normally do.
"We will actually have an advantage over implanted retinal prosthetics," 
says Lowery. "Most of our sharpest vision takes place in a tiny portion of 
the retina rich in rods and cones known as the fovea. The fovea is only 
about a square millimeter in size, so intraocular prosthetics must also make 
use of retinal tissue more associated with peripheral vision. The brain area 
that actually processes central vision is twenty-five times larger than the 
retinal tissue it services, however, which gives us potentially twenty-five 
times the resolution of a retinal implant."
Lowery and his team hope to initiate their first clinical trials by the end 
of 2016. "We plan to begin with four tiles, but eventually we hope to 
increase that number to eleven," he states. "We also hope to reach ten 
frames a second in transmission speed." According to Lowery, the resolution 
could also potentially be enhanced many times over by coating the electrodes 
with special hormones called brain-derived neurotropic factors. "Instead of 
poking the brain neurons with electrodes, these chemicals would actually 
encourage the neurons to reach out and make contact and new connections, as 
though the electrodes were other brain cells."
Also according to Lowery, realistic depictions of the world around us are 
not the be all and end all of Gennaris's potential. "We already have facial 
recognition that does a great job of identifying people. Imagine a special 
icon representing your husband or wife, others for each of your children 
that could include emotional content, smiles, tears, and the like. Direction 
and distance markers for doors, elevators, and windows would also be 
possible. We could even generate runway-light-like guidance systems to help 
navigate a warren of unfamiliar corridors, pointing out obstacles along the 
way."

With Best Regards,
God Bless,
Alan
Plantation, Florida