Tapping an Unlikely Source: Scientists use mouth membrane to construct corneal-surface transplants

Japanese researchers have repaired the corneas in four people whose vision had been nearly wiped out by eye disease. But rather than transplant corneal tissue, the scientists fashioned a new outer layer for the damaged corneas from bits of tissue taken from each patient’s own mouth. More than a year later, the transplants are providing much-enhanced sight for the patients.

Cornea replacement is the foremost success story of the transplant era, thanks largely to the tissue’s characteristics. Being transparent, the cornea lacks blood cells and so doesn’t prompt immune rejection. Still, cornea transplants from dead donors have thrived only when a recipient has a reserve of corneal stem cells, which reside where the cornea meets the white of the eye.

Normally, these cells continuously renew a clear layer over the rest of the cornea—a shield over a shield. While inadequate to rebuild a damaged cornea from scratch, lingering corneal stem cells can often team with a transplanted cornea to maintain the outer layer and preserve sight.

However, a person whose outer corneal layer is severely damaged by heat, chemicals, or certain diseases may have no stem cells in reserve. In these patients, corneal transplants typically fail. To help this group, ophthalmologist Kohji Nishida of Osaka University Medical School and his colleagues turned to a stem cell that forms the membrane that lines the mouth.

The researchers collected tiny sections of membrane from inside the cheeks of four people who had extensive damage in both eyes from complications of a rare ailment called Stevens-Johnson syndrome. The tissues were cultured in the lab, where they grew into sheets about 25 millimeters across.

After removing the damaged outer-corneal layer of one eye of each patient, the scientists transplanted a membrane sheet onto the remaining corneal tissue. In all four people, the transplants immediately took hold, growing across the cornea’s surface, the researchers report in the Sept. 16 New England Journal of Medicine.

All the patients had started with vision of 20/2,000 or worse. Within 10 weeks after surgery, the transplants restored vision to 20/300, 20/100, 20/50, and 20/25 in the transplanted eyes. The improvements remain 14 months after surgery.

Attempts to replace corneal stem cells with similar cells from a patient’s good eye or from that of a related donor have shown promise, but many have failed after a few years, says ophthalmologist Ivan R. Schwab of the University of California, Davis Medical Center in Sacramento. “While I applaud the [new] research,” he says, “I’m only cautiously optimistic.”

Meanwhile, scientists don’t know why the oral stem cells might take on the role of corneal stem cells. Schwab suspects that cells and signaling molecules that the lower corneal layers naturally send to the surface influence the transplanted cells. It may be an example “of the body talking to itself,” he says.

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