Stem Cells Repair Damaged Corneas in Mice

FRIDAY April 10, 2009 -- Stem cells injected into the eyes of mice with defective corneas returned the corneas to a more normal appearance, a new study has found.

Researchers hope the procedure might one day be an alternative to corneal transplants in humans. About 40,000 such transplants are done each year in the United States.

"The stem cells took the scar-like matrix, remodeled it and made it more like normal," said senior investigator James Funderburgh, an associate professor of ophthalmology at the University of Pittsburgh. "We were surprised and delighted."

A report on the study is in the April 9 online edition of the journal Stem Cells.

The cornea is the transparent, front layer of the eye that serves as a protective barrier and, along with the lens, helps focus light. Corneas can develop scar tissue from chronic inflammation caused by infections or other conditions and by injuries, such as chemical or thermal burns or other trauma.

Scar tissue can cause the cornea to lose its transparency, preventing it from focusing light, and this can lead to a loss of visual acuity, including cloudy, hazy vision sometimes described as looking through frosted glass.

"The only effective therapy is corneal transplant," Funderburgh said.

Several years ago, using human cadavers, Funderburgh and his colleagues collected stem cells from the stroma, a matrix of collagen fibers that gives the cornea its strength.

In a healthy cornea, the collagen fibers run parallel to each other and are highly organized. In a damaged cornea, the matrix is irregular and disorganized, he said.

After growing stem cell cultures in the lab, the researchers injected the stem cells into the eyes of mice bred to have defective corneas that mimic scar tissue in humans.

After three months, the stem cells had regenerated the collagen fibers, making the damaged corneas in the mice look normal, the researchers reported. After one year, the mice corneas still appeared normal.

Stem cells are being used in clinical trials in humans to regenerate other eye tissues, including the epithelium, said Dr. Richard Bensinger, an American Academy of Ophthalmology spokesman.

But he cautioned that the scar-like condition the mice have is different from scar tissue caused by an injury or infection in humans. The mice corneas contained "biochemically deficient tissue" that's missing a protein needed to correctly form the collagen matrix, he said.

A human eye with scar tissue is not missing a protein and has other issues.

"In mice, replacement of the missing protein restores the normal corneal architecture," Bensinger said. "Traumatized corneas in humans are not missing something but have too much of a broad array of proteins causing the scar. Treating such a scar with a replacement protein which happens to be one they already make is not likely to change the character of the scar."

Dr. Ivan Schwab, professor of ophthalmology and director of the Cornea and External Disease Service at the University of California, Davis, was more optimistic.

"Although many steps remain to bring this to a human trial level, this is a real biological step," Schwab said. "Not only does this provide new avenues for possible development of corneal tissues, but it offers new avenues for other tissues as well. This team is to be applauded for outstanding work."

Funderburgh said it will take about two years to develop stem cell cultures that would be suitable for testing in humans, after which they hope to begin clinical trials.

To date, there has not been a shortage of corneas for transplantation in the United States, although there have been shortages in countries where religious and cultural taboos discourage donating or using body parts from the dead.

However, the LASIK corrective eye surgery renders corneas unsuitable for transplantation, which could mean a shortage in years to come, Funderburgh said.

Transplanted corneas have a low risk of rejection, and patients don't even need to take immunosuppressant drugs, Bensinger said. But because of the characteristics of scar tissue, people with corneal injuries are often not good candidates for corneal transplants, and rejection rates among them are higher, he said.

More information

The U.S. National Eye Institute has more on the cornea.

Posted: April 2009


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