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Closer to fooling the eye

Special to The Times

THE cornea of the eye seems so simple a structure -- yet it’s so important and so tricky to re-create in a lab. It is the eye’s protective window, keeping out dirt, debris and germs. It’s a lens that helps focus light so that we can see.

But when a cornea becomes cloudy or scarred from disease, injury or infection, the path of light into the eye can be distorted or blocked, resulting in blindness.

Transplanting human corneas from cadavers can restore someone’s vision. But because of a tissue shortage, only 100,000 corneal transplants are performed worldwide annually -- serving just 1% of the 10 million people who are stricken with corneal blindness. This shortfall, as well as problems with such transplants even when available, has spurred the quest for an artificial version of one of nature’s masterpieces.

“The holy grail is a synthetic implant that is as strong, clear and flexible as a natural cornea, that would fully integrate into surrounding tissue and last forever,” says Jean-Marie Parel, head of the Ophthalmic Biophysics Laboratory at the Bascom Palmer Eye Institute in Miami. “That way, we could implant this at any time, day or night, without having to hope that someone died.”

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Bioengineers are making significant progress. They predict that within a few years we could have cornea substitutes that slip over the surface of the eye as easily as contact lenses and mesh neatly with surrounding tissue to form a protective barrier against the outside elements.

Such devices would be of great use even in the U.S., where the shortage of corneal tissue isn’t critical but where other problems exist. More than 46,000 Americans undergo cornea transplants each year. They must use steroidal eye drops (which have side effects) to prevent tissue rejection and endure a lengthy recovery period of up to six months; sometimes they are left with astigmatism, an uneven contour of the cornea that causes blurriness. Up to 10% of corneal transplants fail.

The new devices are also expected to improve on two artificial corneas that are already approved by the Food and Drug Administration: one called the Dohlman, developed at Harvard University, and a newer one, the AlphaCor, created by Australian scientists. In both cases, patients can develop inflammation and infections, and sometimes the devices pop out. In the case of the Dohlman implant, human donor tissue is required. For these reasons, they are used only as a last resort for people who have repeatedly rejected natural corneas or who can’t receive donated tissue because of severe eye diseases.

The cornea is a highly organized group of cells and proteins arranged in five basic layers. The outermost layer -- the epithelium -- blocks foreign material and bacteria, and absorbs oxygen and nutrients from tears. It is filled with thousands of tiny nerve endings that make the cornea sensitive to pain.

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Other structures include the Bowman’s layer and the stroma, both composed mainly of water and collagen, which give the cornea its strength and elasticity and help preserve its transparency. Below the stroma is Descemet’s membrane, a thin sheet of tissue that protects against infection and injury. Finally, there’s the innermost endothelium, which prevents excess fluids from collecting in the cornea.

Researchers at the University of Ottawa Eye Institute in Canada are working on one artificial device that has many of the properties of the real thing. It is made from a strong, synthetic collagen gel (derived from pigs), with a high water content, that forms a network of ultra-thin, near-invisible fibers. It is engineered in a way that allows it to knit seamlessly with the surrounding tissue during the healing process.

When the device was implanted into pigs, dogs and rabbits, cells from the animal grew over the device to form a new epithelial surface. Nerve cells grew into it too. Both are huge steps forward, says Parel. The epithelial cells form a protective barrier. The reattached nerves tell the brain when to blink and generate tears so that the cornea won’t dry out.

This repopulation with human cells can occur because the device is made of substances that are engineered to structurally resemble natural tissue -- and thus, the body is fooled into believing it is the real thing, says May Griffith, a cell biologist with the University of Ottawa research team. The scientists hope to begin human tests within the next year.

Scientists at Stanford University in Palo Alto have taken a slightly different approach. Their artificial cornea is made of two interwoven networks of water-based synthetic gels designed to create a structure that is strong and flexible. Collagen is placed at the outer edges to help mesh the natural and artificial tissues and promote the growth of a clear layer of epithelial cells over the implant.

A 2006 study in which the devices were implanted into rabbits showed they were compatible with the eye and weren’t rejected by the recipients. The artificial corneas integrated with the surrounding tissue, and epithelial cells stuck to the implants’ surfaces.

Though these results are encouraging, more animal studies are needed to confirm them, says Dr. Christopher Ta, an ophthalmologist and co-leader of the Stanford team. Human tests are still years away.

British researchers are taking yet another tack, using adult stem cells harvested from corneas to stimulate a covering of epithelial cells on their man-made implants. The implants are made of polymers similar to the fluid-absorbing plastics used in soft contact lenses.

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In recent tests using cow eyes, scientists successfully coaxed the epithelial cells to grow over the synthetic corneas. The next step is to test the technology on live rabbits, says Nigel Fullwood, a cell biologist at the University of Lancaster, where the work is being done.

Though only several dozen scientists around the world are working on this technology, Griffith is optimistic that a corneal substitute will soon be available. “We hope to get this out in the next five years,” she says.

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Less invasive surgery in focus

Although corneal transplants can restore vision, recovery takes up to six months and patients can be left with astigmatism that gives them blurry vision. A new surgical procedure, known as deep lamellar endothelial keratoplasty (DLEK), has fewer complications, a shortened recovery time, no additional astigmatism and less risk for eye trauma. The surgery entails transplanting a thin piece of donor corneal tissue (containing just two cornea layers, the endothelial cells and stroma) instead of the whole cornea. It also requires just a small incision rather than completely opening the front of the eye. Eye surgeons estimate that DLEK could replace nearly half of the whole-cornea transplants performed in the U.S. each year.

-- Linda Marsa


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