BY CZERNE M. REID
An interdisciplinary team of experts is working to reverse the effects of age-related macular degeneration -- the leading cause of blindness among Americans over age 65. The researchers plan to use eye tissue transplants for patients who still have some vision and prosthetic chips for those who have lost all vision.
"This is a very optimistic and ambitious project," said chemical engineer Stacey Bent, who with ophthalmologist Harvey Fishman jointly leads the research efforts.
On Saturday, Fishman presented the first complete design for a chip that functions like the natural retina of the eye. It uses chemicals to transmit nerve impulses to the brain. He spoke at the annual meeting of the American Academy of Ophthalmology in Anaheim. Also this week, two of Bent's graduate students, Christina Lee and Neville Mehenti, are presenting the group's work at the annual meeting of the American Institute of Chemical Engineers in San Francisco.
Optimistically, human trials of the tissue transplant could begin within the next six months, Fishman said. The retinal prosthesis is a longer-term project -- trials could begin in two to three years. The team already has successfully implanted prototype devices into animals and is refining the surgical techniques to prevent complications such as bleeding or retinal detachments.
In a healthy eye, vision occurs when light-sensitive cells in the retina convert light into electrical signals that 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 those patients, some underlying cells remain alive although the cover layer has degraded. The team is recreating the protective cell layer using cells and tissues from other parts of the eye. This involves removing the tissue that normally covers the eye lens and using it as a support membrane on which to grow healthy cells taken from the iris. The iris cells are capable of growing into different types of cells that perform different functions. The lens tissue can be replaced with an artificial lens, as is routinely done during cataract surgery. The newly created layer would then be transplanted into the retina. Since only the patient's own tissues and cells are used, this type of transplantation reduces the possibility that the immune system will reject the implant.
The major challenge to this approach is getting the transplanted layer of cells to look and act like the naturally occurring layer. The cells need to be densely packed onto the membrane and perform the necessary feeding and waste-removal functions. Bent and her team of engineers are devising ways to modify how the iris cells cluster on the surface of the lens capsule tissue using some of the same techniques used to make patterns on a computer chip. They also are monitoring the biological function of the cells. At the same time, the surgeons are developing and testing microsurgical techniques for transplanting the newly developed materials into the eye.
"That's actually why it's such a fun project, because it's not just academic," said Bent. "These problems have to be approached in both directions -- the engineering and the medical side of it." Fishman says that without the contributions of experts such as ophthalmology Professor Mark Blumenkranz in retinal surgery, and others in fields such as physics, chemistry and engineering, the work would not have been possible. "This is the new generation of super highly collaborative scientists," he said.
'The holy grail of prostheses'
For the remaining 20 percent of patients with age-related macular degeneration, all the light-sensitive cells have died. In those cases, a pinpoint-sized electronic device capable of receiving light and translating it into nerve-stimulating signals would be implanted into the eye. Bent called it "the holy grail of prostheses -- it's coming up with something electronic that could take the place of something that's naturally there but is having problems because of disease."
Bent said the investigators are working toward the most "physiologically correct" kind of prosthesis. They want to stimulate the nerve cells with chemicals, in the same way that neurons work naturally. When hit with light, the prosthesis would release a burst of neurotransmitter chemicals through a system of tiny valves. Those chemicals would stimulate the neurons.
Retinal prosthetic devices developed by others over the last five years stimulate the nerve cells with metal electrodes. But Fishman is concerned about the long-term effects of constantly hitting cells with electrical currents. The early retinal prostheses also have been relatively large and positioned far away from the neurons, so the electricity affects everything in the vicinity rather than focusing on the nerve cells. Fishman compares the process to hitting the nerve cell over the head with a large electrode hammer. "Maybe we can tickle the retina instead," he said.
To do this, the researchers will develop a chip from soft polymer material that can conform to the curvature of the back of the eye. This material would be better suited to the task than a traditional silicon chip. Researchers are developing techniques for extending the nerve cell branches so they can be close enough to the chip to be stimulated individually.
The initial work on the project was made possible by a grant from Bio-X and continued through industry support from VISX Inc., a California-based company that specializes in the design, manufacture and marketing of proprietary laser vision correction technologies. The investigators have applied for additional funding from the National Institutes of Health to continue their work.
The new technologies being developed to solve vision problems may find applications in other areas of medical research for conditions that affect many more people. "We are developing tissue engineering ways to regenerate nerve cells and to release drugs in very selective ways," Fishman said. "This has tremendous implications for the field of drug delivery in the eye and other parts of the body including the brain." He believes that neurodegenerative diseases such as Parkinson's and Alzheimer's may benefit from the technologies being developed.
Czerne M. Reid is a News Service intern.
Stanford Report, November 19, 2003