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Gene discovery could yield treatments for nearsightedness

DURHAM, N.C. -- Myopia (nearsightedness) is the most common eye disorder in the world and becoming more common, yet little is known about its genetic underpinnings.

Scientists at Duke University Medical Center, in conjunction with several other groups, have uncovered a gene associated with myopia in Caucasian people from several different regions, including Dutch, British and Australian subjects.

Their work was published in Nature Genetics online on Sunday, Sept. 12.

Myopia happens when the focal point of an image falls just short of the retina at the rear of the eye, causing blurred distance vision.

Often the discovery of a gene still means that many years could pass before a treatment becomes available. However, gene therapies are already working well in some eye conditions, and myopia may be a good candidate condition for gene repair.

"The eye is already an organ of choice for gene therapy, for example, because the eye's small volume and self-contained area allow the therapy to remain inside the eye in a concentrated volume," said lead author Terri Young, M.D., professor of ophthalmology, pediatrics, and medicine, and a researcher in the Center for Human Genetics at Duke. "In addition, the eye's accessibility lets clinicians observe the effects of treatment over time with noninvasive methods that can illuminate and test the retina and other eye structures."

While many cases of myopia are mild, about 2 to 3 percent are pathological cases with retinal detachment, premature glaucoma, macular bleeding, and glaucoma leading eventually to blindness, said Young, who has spent over a decade studying the severe form of myopia.

Up to 80 percent of people in Singapore have myopia, while about one in three Americans has the condition. Countries with a high prevalence of nearsightedness have a hard time finding fighter pilots, to give one example of how myopia affects a population.

There is an antidote for the condition. "People need to go outside and look to the horizon," Young said. "Today's near work forces our eyes to constantly be in tension to focus on near objects reading papers and watching monitors. We also watch TV, work in cities with high buildings, drive in heavy traffic, and generally have fewer chances for distant views, especially in urban areas. These factors affect children with developing vision, as well as many adults."

Working with a large group of researchers, Young, co-lead author Pirro Hysi of the Department of Twin Research and Genetic Epidemiology of Kings College in London, and colleagues found several distinct spellings of DNA code near the RASGRF1 gene that had a strong association with focusing errors in vision. These findings were validated in six other Caucasian adult groups in a total of 13,414 subjects.

"Because RASGRF1 is highly expressed in neurons and the retina, it is crucial to retinal function and visual memory consolidation," Young said.

When the scientists created mice that were missing the correct gene, these mice showed changes in their eye lenses.

"This was biologically convincing," Young said. "The RASGRF1 provides a novel molecular mechanism to study so that we can work to prevent the most common cause of visual impairment."

Young has also led a team that found a different gene -- CTNDD2 -- related to myopia in Chinese and Japanese populations. That work included researchers from the Duke Center for Human Genetics, the Duke-National University of Singapore (NUS) Graduate Medical School in Singapore, and the National University of Singapore. In many Asian countries, a majority of people have myopia.


Contact: Mary Jane Gore
Duke University Medical Center

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