Eye Cell Implant Research Offers Hope for the Blind

Researchers are developing a bold and unusual new type of transplant operation that they think may eventually be able to restore vision in individuals blinded by the loss of photoreceptor cells--the cells in the eye that convert light into an electrical signal transmitted to the brain.

The project is one of a group of studies initiated during the last three to four years in which new technology in transplantation is being applied to treatment of the eye--one of the most complex and sophisticated organs in the human body. “We are on the brink of a new era” in the treatment of blindness, said electrophysiologist Alan Adolph of the Retinal Foundation’s Eye Research Institute in Boston.

At least 5 million Americans suffer severe or complete vision loss resulting from the death of such cells caused by retinitis pigmentosa, macular degeneration and other genetic diseases.

Neurobiologists Martin S. Silverman and Stephen E. Hughes of Washington University in St. Louis have transplanted into blind rats fragile photoreceptor cells from other rats and even from human eyes. The cells have not only survived, but have also produced chemicals important to vision.

The scientists believe, but have not yet proved, that the transplanted cells restore at least partial vision.

The new research complements recent reports from two other groups who have transplanted a different type of cell into the eyes of rats. Those researchers have shown that the transplanted cells prevent deterioration of photoreceptor cells caused by retinitis pigmentosa and related diseases.

Other researchers are cautious in their interpretation of the new transplant results because they do not wish to produce undue optimism in patients with eye diseases. “The layers of questions that remain to be answered are huge,” said Jeanette Felix, director of science for the RP Foundation Fighting Blindness in Baltimore. “However, the potential is obviously very impressive.”

“It’s quite exciting. . . . It looks like a real advance,” added Adolph.

Researchers stress that the crucial step now is repeating the transplant experiments in cats and primates, where the effectiveness of the procedures in stabilizing or restoring visual function can be more thoroughly evaluated. Such experiments are just now beginning, and two or three years may be required before results will be apparent.

But if the transplants can be shown to function in primates, Felix said, “that will certainly take us a huge step closer” to experimentation in humans.

The new research on the eye was inspired by the success of neurologists in transplanting fetal tissues into animal brains to reverse degenerative diseases such as Parkinson’s and Alzheimer’s, according to neurologist James E. Turner of the Bowman Gray School of Medicine of Wake Forest University in Winston-Salem, N.C.

Nourishing Cells Transplanted

In those experiments, researchers have shown that the transplanted embryonic tissues can make connections to existing cells in the brain and restore function. “The question then was: Cannot that (approach) be transferred to the visual system, the eye particularly and most particularly the retina?” Turner said.

Last year, Turner and his colleagues reported that they had developed a technique for isolating and transplanting a particular kind of cell called the retinal pigment epithelial cell. These dark brown or black pigmented cells physically support and nourish the photoreceptor cells. When the epithelial cells die off in diseases such as macular degeneration, the photoreceptors do not receive nourishment and they also die, producing blindness.

Turner found that injecting a suspension of epithelial cells into the eyes of rats whose vision was degenerating prevented further loss of photoreceptor cells. That result has been confirmed by neurologist Peter Gouras and his colleagues at Columbia-Presbyterian Medical Center in New York City.

But transplanting the photoreceptor cells themselves is a more complicated procedure--so complicated that many researchers did not even consider it possible, Silverman said. The problem is that cells in the ultra-thin photoreceptor membrane must be kept in precise alignment with each other during the transplant procedure so that, if the operation is successful, the brain will be able to interpret the visual signals.

Silverman and Hughes’ success came, they report in the current issue of Investigative Ophthalmology & Visual Science, because they developed a technique to maintain this alignment.

Silverman and Hughes remove the entire retina from an 8-day-old rat and flatten it onto a gel that serves as a support. They then use a very sharp knife to cut off each of the four layers that lie above the photoreceptor cells. They are left with a layer, about as thick as an index card, of photoreceptors on the gel.

Working through a small incision in the cornea of rats that have been blinded by exposure to intense light, the researchers gently detach the retina and insert the layer of photoreceptors beneath it. The retina then reattaches itself as the gel dissolves and the cornea heals.

“It works beautifully,” Silverman said. “It appears that photoreceptors are almost ideal neural tissue to transplant.”

Silverman and Hughes have shown that the grafts survive for at least six months, the length of the study, and that they are metabolically active, consuming sugars and producing the vision chemicals normally produced by photoreceptor cells. But demonstrating that they restore vision is more difficult.

The pair are now examining the grafts microscopically to determine if the transplanted cells have grown into physical contact with the nerve cells that would carry a message to the brain. He would not reveal the results of those studies, “but I can tell you it is going very well.”

The ultimate test will be to determine if function is restored. But because rats’ vision is not very good to begin with, and their brains are very small, they are not good models for such a test. Silverman has begun collaborating with Turner to carry out the procedure in cats and primates, which have visual systems more like that of humans.

Such animals can be subjected to vision tests that are the equivalent of asking humans to look at an eye chart. Researchers throughout the country are excitedly awaiting the results of those studies.

The seemingly unlikely possibility that the transplanted photoreceptors can make the proper mechanical linkage to the brain is supported by unusual experiments conducted by neurobiologist Raymond Lund of the University of Pittsburgh School of Medicine.

Lund has recently transplanted embryonic rat retinas directly onto the surface of rat brains near the brain’s visual center. He found that the retinas apparently made the correct physical connection to the brain. When light was shined upon the transplanted retinas, for example, the animal’s normal eyes contracted--the correct physiological response dictated by the brain.

The fact that connections occurred in his own experiments, Lund said, suggest that they could occur as well in Silverman’s.