Study Links Gene to Serious Eye Disease

Researchers identify robust association between the two

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By Melissa Lee Phillips
HealthDay Reporter

WEDNESDAY, Aug. 25 (HealthDay News) -- Researchers have identified a gene linked to an inheritable eye disease that affects 5 percent of U.S. residents over 40 and is the most common cause for transplants of the cornea.

The genetic disorder, known as Fuchs corneal dystrophy (FCD), causes tiny bumps on the cornea -- the thin, clear membrane that covers the front of the eye -- that can lead to blurred vision, eye pain and swelling and, in advanced cases, to a marked loss of eyesight.

"The association we found is novel and identifies the first gene that is a major contributor to FCD," said study senior author and research team leader Dr. Albert Edwards of the University of Oregon in Eugene, whose report appears in the Aug. 25 online version of the New England Journal of Medicine.

Previous work has identified three genes that are associated with rare subtypes of Fuchs, but the genetic basis of the most common form of the disease was not understood.

The authors analyzed the genomes of 280 people with Fuchs and 410 people without the disease. They found that people with particular versions of a gene called transcription factor 4 (TCF4) were much more likely to develop FCD.

People with one copy of a high-risk version of TCF4 were five times more likely to develop FCD as were people without one of these versions; those with two copies were 30 times as likely to develop the disease.

The researchers are not sure through what mechanism altered forms of TCF4 might cause FCD, although they suspect that it may involve a protein called E2-2. TCF4 encodes E2-2, which is involved in cellular growth and differentiation and is expressed in the developing cornea.

Only a small percentage of patients with FCD require a corneal transplant, according to the researchers, but in advanced cases causing major vision loss, it is the standard treatment.

The researchers have identified a "robust association" between TCF4 and the development of Fuchs, but they have not yet shown a causal relationship, said Dr. John Gottsch, a professor of ophthalmology at the Wilmer Eye Institute at Johns Hopkins University, who in other studies has identified chromosomes linked to rare FCD subtypes. It's not clear how different versions of TCF4 might lead to the development of the disease, he said.

According to Edwards, understanding the genetic predisposition for FCD may be helpful for selecting participants for future studies on the condition, especially for research aimed at understanding if this genetic risk predicts its progression. Developing a genetic test for FCD could also help surgeons avoid transplanting donor corneas that might eventually develop the disease, he said.

"The real impact of what we've done is to determine the biological underpinnings of the disease," Edwards said in a university news release. "We've identified a protein that is probably involved, and that will allow us to, hopefully, identify a method to prevent people from losing their vision."

More information

Find out more about Fuchs corneal dystrophy at the U.S. National Eye Institute.

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