Fetal cells tested as remedy for common eye disease

January 30, 1997

For the first time in the United States, a team of ophthalmologists from the University of Chicago Medical Center has transplanted fetal retinal pigment epithelial (RPE) cells into one eye of a woman suffering from age-related macular degeneration in an innovative attempt to cure this common and debilitating disease.

On January 29, 1997, the six-person team led by J. Terry Ernest, MD, professor and chairman of ophthalmology at the University of Chicago Medical Center, and retinal surgeon Samir Patel, MD, assistant professor of ophthalmology, inserted a one-millimeter microsphere containing about 250,000 fetal eye cells under the patient's retina in a two-hour surgical procedure.

"If the transplanted cells perform in the ways we expect them to, and it will be months before we are certain of that, it could provide us with the first truly effective treatment for the major cause of blindness in the elderly," said Dr. Ernest.

An estimated 3 million people in the United States suffer from macular degeneration; 20 to 35 percent of all people older than age 75 have various stages of the disease. Autopsy studies indicate that most people over 70 already have some evidence of it.

There are 200,000 new cases each year, making it as common as breast cancer. That number could double by 2030 as the population ages.

The disease causes gradual loss of central vision by damaging the RPE cells that underlie the macula, the small region of the retina responsible for fine detail at the center of the field of vision. Patients first lose the ability to see details and are soon unable to read. They describe the early stages as "living in a veiled world, seeing everything through a haze," which progresses to increasing loss of vision as the disease spreads.

Although laser treatment can sometimes slow the spread of some forms of the disorder, there is no proven effective treatment for the advanced stages of macular degeneration.

The first patient to undergo the fetal cell transfer was an 80-year-old suburban woman who, although legally blind, remains an active volunteer at the University of Chicago Hospitals. She has suffered progressive vision loss for more than five years that could not be controlled by the standard treatments such as laser therapy.

Her vision in her right eye is currently slightly worse than 20/200, the threshold for the legal definition of blindness. Her left eye is significantly worse than 20/400, meaning she can see at 20 feet what the normal person can see at more than 400.

Only her left eye, which has suffered the most damage, was treated. The fetal cells, collected after a medically necessary, second-trimester abortion, have been specially prepared and grown in the laboratory for use in transplantation. The researchers used fetal cells because they grow rapidly and are less likely than mature cells to provoke an immune response.

Although this was the first time this approach was used to treat macular degeneration in the United States, a Swedish research team used a slightly different method to treat a small series of patients there. That attempt did not alter the patients' eyesight, probably because the cells did not multiply as the researchers had expected.

A team from the University of Rochester used a different type of fetal eye cell to treat a rare inherited eye disorder known as retinitis pigmentosa. They report "somewhat improved sight" in four of eight patients.

The Chicago physicians spent three years in the laboratory developing systems to stimulate the spread of fetal cells, before and after transplantation. They devised a technique to grow and insert the cells in tiny spheres of a matrix containing substances that stimulate cell growth.

When studied extensively in animal models, this approach led to vigorous proliferation of the transplanted cells both in culture and after insertion under the retina. A few weeks after the surgeon inserted the sphere, the cells spread out to form the desired single layer, which replaces damaged cells.

"We've learned how to grow these cells quite successfully in culture and implant them in different animal models," said Dr. Ernest. "We hope to see the same sort of growth in this first human trial."

To restore vision, the cells must not only grow and replace the tissue damaged by the disease, they also must connect with and support the light-sensitive photoreceptor cells of the retina.

Because there is no animal model for age-related macular degeneration, this has not been tested. "The only way to assess the clinical effects of the procedure is through human trials," said Dr. Ernest.

According to Dr. Patel, the surgical procedure, though very delicate, "is not terribly different from what retinal surgeons do routinely." Using a microscope, he cut three tiny holes in the eye to admit surgical instruments and a fiber-optic light source. He used a micro-pipette to place the tiny ball of cells within the eye then used miniature forceps to slip it under a small incision in the retina at the edge of the macula.

During the next few weeks the cells should multiply and expand to restore the damaged macula.

"We have done similar operations hundreds of times, for complications of diabetic retinopathy or for a detached retina," said Dr. Patel. "The novelty in this case, and the difficulty, lay in creating an appropriately sized retinal opening and inserting the microsphere without damaging either the retina or the ball of transplanted cells. Improvements in instrumentation should make this a relatively simple procedure for experienced retinal surgeons."

Within a few weeks after surgery, the researchers can tell if the implanted cells are growing as planned, and whether the recipient's immune system has mounted an attack on them--which is unlikely. The eye is a "privileged" site, with limited immune scrutiny.

But the transplanted cells will not produce any beneficial effects on the patients' eyesight for at least three months.

Although the researchers anticipate performing this procedure on an outpatient basis under local anesthesia, they decided to use general anesthesia for the first patient and to keep her in the hospital overnight for observation.

"It was an honor to be the first," she said the morning after surgery. "I'm excited; it seems like a dream that there is a possibility that something might help." Her only complaint was that her doctors asked to sleep facing down for three nights.

She was discharged at 11 a.m. on January 30, 1997, the day after her operation. She will return to the clinic for checkups once a week for three months. The University's Institutional Review Board, after thorough review of the proposal and consent process for both the donor and recipient, approved the research protocol. The team will perform five of these experimental procedures. Patients who participate will not be charged. If the procedure proves effective, it will cost about $10,000, Dr. Ernest said.

The availability of appropriate fetal cells is quite limited. Only about 5 percent of all abortions are performed during the second-trimester. At most centers they are offered only when medical reasons require termination of the pregnancy or the fetus has a severe chromosomal abnormality. As a regional referral center for high-risk pregnancies, the Hospitals perform about one per month.

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