Research Profile - A clear-eyed answer

A Montreal eye surgeon and researcher is working on a way to repair all-too-common damage to the cornea, to ease pain and restore sight.

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Growing older is a gains-versus-losses proposition.

You gain wisdom, but lose youthful exuberance. Gain ability, but lose flexibility. And while we are going about our lives and gaining valuable experience, we are also quietly losing a key component of clear vision: our corneal endothelial cells.

"The endothelium is the thin layer of cells covering the posterior surface of the cornea," explains Dr. Isabelle Brunette, a Professor at the University of Montreal and a surgeon at the Maisonneuve Rosemont Hospital.

"We're born with 4,000 cells per square millimetre and we lose them because they do not replicate. It's attrition over time, so that when you're around 80 years old you might only have 2,000 cells per square millimetre. And if there's an accident or there's a surgery on the eye or inflammation, you can lose more cells. We need 400 to 500 minimum endothelial cells for a cornea to survive."

These cells play a vital role, says Dr. Brunette. They pump out water to keep the cornea naturally dehydrated and transparent. If they fail to function properly, water collects in the cornea, thickening it like a wet sponge and causing white bubbles to appear. It's a painful condition because of the high concentration of sensitive nerves in the cornea.

The two major causes of endothelial dysfunction are age-related: complications from cataract surgery and Fuchs' Endothelial Dystrophy, a condition that tends to do its damage when people are in their 50s and 60s. Not surprisingly, with most Western nations dealing with aging populations, the number of people who need corneal transplants for endothelial dysfunction has jumped and is expected to grow greater still. While eye bank donations provide a source for the tissue for corneal transplants, the wait, depending on where you live, can be lengthy.

"It varies," says Dr. Brunette. "Certainly here in Quebec the wait can be years."

To address the problem, Dr. Brunette and her colleagues Drs. Lucie Germain and Stéphanie Proulx of the Laboratoire d'Organogénèse Expérimentale (LOEX) at Laval University are working on a new approach to corneal transplantation that could circumvent the need for eye bank corneas. She is developing a tissue engineering process that, when possible, would allow use of patients' own cells to restore their sight.

Corneal transplantation techniques have advanced considerably in the 21st century. The classic approach in use as recently as five years ago was to replace the cornea in its full thickness with a donated one, even if only the endothelial layer needed repair. Dr. Brunette likens that to "replacing a whole arm when you only have a problem with the middle finger."

Currently, eye surgeons like Dr. Brunette are removing the diseased endothelial layer and replacing it with a "half thickness cornea" – a process that requires no suturing of the graft and has less chance for complications.

Funded by the Canadian Institutes of Health Research, Dr. Brunette is now shifting that paradigm: she and her group have found a way to rebuild a person's endothelial cells and replace them specifically.

"Essentially, it involves taking a biopsy from the corneal endothelial cells of the diseased cornea and putting them in culture. We reconstruct the endothelium through tissue engineering and then transplant it back into the eye." Preclinical test results are encouraging: "It's working well – the corneas are crystal clear."

Because the endothelium is jelly-like, replacing it in the cornea requires a thin "carrier" that Brunette fashions using a femtosecond laser. The laser sends pulses at a speed of one millionth of a nanosecond, allowing her to shape the replacement endothelium to fit the patient precisely. This work is done in collaboration with the Institut national de la recherche scientifique at Varennes, Quebec.

Dr. Brunette sees three major improvements with her approach. "First, tissue engineering may permit to eliminate the risk of disease transmission from donor tissue. Second, you don't have to deal with the waiting list for eye bank corneas. Third, it's your own tissue and your own cells, so there's no rejection."

Dr. Brunette expects that she is three years away from using this new technique in the clinic. "The next step will be to demonstrate that our transplant can remain clear for longer periods of time and then we will go to Health Canada for approvals for clinical testing."

By the numbers:

• Forty-two percent of the 57,000 corneal transplantations performed each year in Canada and the United States are done to replace the corneal endothelium.
   
• Between 15-25% of corneal transplants are rejected by the body, and rejection can happen any time. Dr. Brunette has a patient whose transplant was rejected 21 years after he received it.
   
• The Eye Bank Association of America, which tracks U.S. eye bank activities, reported the number of corneal transplants increased 11% in 2007 from 2006.

"Right now with the improvement that we're expecting with the research ... we are aiming at no rejection and optimal optical quality. "