Laboratory-grown corneas may benefit research

December 9, 1999
Web posted at: 5:30 PM EST (2230 GMT)

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By Mari N. Jensen

(WebMD) -- Artificial corneas that work much like real ones have been grown in the laboratory for the first time. These corneas could someday be used to replace live animals in laboratory tests, serve as a model for studying how wounds heal, and may eventually lead to bionic corneas for transplants, suggests a report in this week's journal Science.

A team of researchers has coaxed human corneal cells into growing, not as part of a living human eye, but on an artificially constructed scaffold of protein. The resulting organism has the same three-layered structure as a human cornea. According to the first tests, these bioengineered corneas mimic how human corneas function -- at least in certain ways that are important for repairing the cornea and maintaining its transparency.

The lead researcher and inspiration for the project is May Griffith, Ph.D., M.B.A., a cell biologist at the University of Ottawa Eye Institute in Ontario, Canada. Griffith wanted a better way to study how wounds heal in corneas. Her goal was to figure out why some laser eye surgery patients had scarring and others didn't. For this, she needed corneas to study, which could be gotten from eye banks.

But the need for corneas that can be transplanted into people takes precedence over the need for corneas for research purposes, so eye banks provide researchers only with the corneas that are too old to be used in transplants. Unfortunately those corneas were also too old to be useful in Griffith's research.

Constructing a cornea

So she and her colleagues at the Proctor & Gamble Company in Cincinnati, the Centre Hospitalier et Universitaire de Quebec in Canada and the University of Tennessee College of Medicine in Memphis decided to try making their own. The team gathered cells from all three layers of transplant-grade corneas and added viral genes that would allow the cells to be grown in the laboratory.

To make an artificial cornea, you have to assemble the layers properly -- it's a bit like baking, Griffith says. The inner layer of the cornea -- the endothelium -- "would be the layer of PAM you put in your baking dish." The next layer is protein scaffolding material with cells mixed in -- much like a batter with chocolate chips, she says. The final layer, the "icing," is made up of the epithelial cells that form the outer surface of the cornea. Then the cornea-to-be is incubated at body temperature for two weeks to give the layers time to knit together.

When done, the bioengineered corneas are transparent and look like contact lenses, says Griffith. Like real corneas, they will activate wound-healing genes when treated with a mildly injurious detergent. When the researchers tried putting stronger chemicals on them, they clouded up much as do rabbit or human corneas.

May replace animal testing

There is hope that the bioengineered corneas will come to replace animals in testing new household products for eye irritation. The Institute for In Vitro Sciences -- a nonprofit organization in Maryland that seeks alternatives to animal testing -- is now collaborating with the Proctor & Gamble Company and Unilever to investigate that possibility, says institute president Rodger Curren, Ph.D.

"One of the biggest concerns with eye irritation is what happens to the cornea," says Curren. "If that gets permanently cloudy, you can't see anything. What you've got here now is a tissue that's just cornea. That could make a good model."

"It's a major advance in terms of developing reconstructed tissue," says Alan Goldberg, Ph.D., director of the Center for Alternatives to Animal Testing at the Johns Hopkins School of Public Health in Baltimore. Goldberg says the new corneas can't replace animal testing yet. Before that can happen, other labs must reproduce the team's work, researchers will have to demonstrate that the lab-grown corneas function like human ones, and the process of growing the corneas must be made economically feasible. "I'm super-encouraged," he says, "but I'm also saying it's not there yet."

Could the bioengineered corneas be transplanted into humans? Not any time soon, says David Hwang, M.D., a corneal transplant surgeon and researcher at the University of California, San Francisco. "We don't have any idea whether the tissue would survive outside the test-tube setting," says Hwang, adding, "At least for the present, these artificial corneas are not going to replace the need for people to donate."