Blind World

Macular Degeneration.
Future neurotransmitter chips for the eye.

June 29, 2004.

By Charles Choi,
United Press International.

Implantable microchips that stimulate nerve cells with puffs of chemicals instead of pulses of electricity are being developed to serve as prosthetic retinas for the blind, scientists told United Press International.

The microchips also could be used as medicine- delivering implants for treating diseases such as Parkinson's.

"It's a very new way to interface with the brain," said lead researcher Harvey Fishman, director of the Stanford Ophthalmic Tissue Engineering Laboratory in California.

Implantable devices that electrically stimulate nerve cells are commonplace, including cochlear implants that help deaf patients hear and deep brain stimulating electrodes that help Parkinson's patients cope with their symptoms.

"When you're stimulating something electrically, you're doing so very indiscriminately," Fishman told UPI. "And you're not stimulating the nerve cell or muscle the way it's normally stimulated."

Nerve cells normally communicate with each other and other cells by releasing chemicals known as neurotransmitters. Instead of just stimulating the cell as an electrical pulse does, neurotransmitters can trigger far more complex reactions.

"When you stimulate electrically, it's like taking a sledgehammer to stimulate a small pebble. With a neurotransmitter, you're basically tickling," Fishman said. "It's a very subtle way of causing changes to occur."

In the past, neurotransmitter chips were simply too difficult to build.

"Technology is just now making it possible to deliver very small amounts of drugs," Fishman said.

He and his team reported their findings online June 24 in the Proceedings of the National Academy of Sciences.

"It's a great idea to attempt to stimulate nerve tissue with chemicals. If it could be made to work, it would have a number of advantages over electrical stimulation," said neuro-ophthalmologist Joe Rizzo, co-director of the Harvard-Massachusetts Institute of Technology Retinal Implant Project and director of the center for innovative visual rehabilitation at the Boston Veteran Affairs Medical Center.

Rizzo's team is separately trying to develop an electronics-based eye prosthesis.

Fishman and his team built a silicon-based chip with four tiny circular openings, each only 5 microns wide or roughly 1/20th the width of a human hair. The microchip can flow droplets of chemicals via these outlets electrically, so no moving parts are needed.

"It's almost like an inkjet printer for the eye," Fishman said. He added the device can draw fluid in as well as out, which researchers could do to withdraw samples in real time to give them a chemical picture of what goes on in living tissues during vital processes.

The team's long-term goal is to develop a treatment for age-related macular degeneration, the most common cause of blindness in patients 55 and older, affecting more than 10 million people in the United States. In a healthy eye, vision occurs when light- sensitive cells in the retina convert light into electrical signals the optic nerve then transmits to the brain. These cells receive nutrients and excrete waste through a thin layer of cells that covers them. In age-related macular degeneration, this life-giving layer degrades over time, leading to the eventual death of the cells beneath. Patients with the disease typically lose central vision.

In about 80 percent of these patients, while the cover layer has degraded, some underlying cells remain alive that could potentially be treated with tissue transplants. For the remaining 20 percent of patients, however, Fishman said a chip implanted on the retina could prove the best option.

"Something like 100,000 patients per year could be helped initially, and then maybe on the order of 50,000 a year," he said.

Rather than just four openings, such a chip would need thousands, each filling in for a lost light- sensitive cell that could then relay visual signals to the brain.

"We'd like to get at least 1,000 points per chip. If we can get 10,000 points, we might be able to stimulate all the cells in the retina. If we could get vision approximating 20/20 vision, that would be a very ambitious goal. But we're talking about returning vision to people who are legally blind, and we really do want to shoot for the stars," Fishman said.

The research was funded by laser vision correction company VISX in Santa Clara, Calif.

"Right now we have 5-micron wide apertures, and we'd like for vision devices to be at least on the order of a micron or less, maybe a half-micron," Fishman added. "We don't see a fundamental limit for that."

The devices in theory could also deliver doses of drugs precisely where they are needed in the body, such as the neurotransmitter dopamine in the brains of patients with Parkinson's disease.

"There are other neurological disorders, like spinal cord injuries, where stimulation might improve function as a prosthesis," Rizzo said. "The excitement is that this is a strategy that would make an artificial system work more like the body normally works. That's always a huge advantage.

"It's a very good and creative idea," Rizzo said. "The real challenge is to develop the engineering to control the release of neurotransmitters and also to protect against excessive stimulation that can damage nerve tissue."

Fishman stressed the devices are still several years away from clinical trials.

"We still have to look at how these chips interact with the body and ensure there's no toxicity or clogging of microchannels," Fishman said.

He added the long-term stability of the molecules in the chip also bears investigation.

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