Gene leads to nearsightedness when kids read

NEW YORK, NY (August 31, 2015) -- Vision researchers at Columbia University Medical Center have discovered a gene that causes myopia, but only in people who spend a lot of time in childhood reading or doing other "nearwork."

Using a database of approximately 14,000 people, the researchers found that those with a certain variant of the gene - called APLP2 - were five times more likely to develop myopia in their teens if they had read an hour or more each day in their childhood. Those who carried the APLP2 risk variant but spent less time reading had no additional risk of developing myopia.

"We have known for decades that myopia is caused by genes and their interactions with environmental factors like reading and nearwork, but we have not had hard proof. This is the first known evidence of gene-environment interaction in myopia," says the study's lead investigator, Andrei Tkatchenko, MD, PhD, of CUMC. The research was published August 27 in PLOS Genetics.

Although it's not yet known how genetic variation at the APLP2 gene causes myopia, Dr. Tkatchenko and his colleagues think the risk variant may increase the amount of APLP2 protein produced in the eye, which in turn may cause the eye to undergo excessive elongation.

They found that mice exposed to a visual environment that mimics reading were less likely to develop myopia when little APLP2 protein was present in the eye.

"By reducing the level of APLP2 in the eye, you can reduce susceptibility to environmentally induced myopia. This gives us an opportunity to develop a therapy to prevent myopia in everyone, regardless of the APLP2 variant they carry," Dr. Tkatchenko says.

Developing such a therapy, however, could take years, as researchers don't yet know how APLP2 levels could be reduced in people. And the therapy would be most effective in young children, before the eye has started to elongate and become myopic.

"Once the eye has elongated, you cannot shrink it, so we would need to identify kids with genetic risk factors as they enter school," Dr. Tkatchenko says. That's not yet possible because there are probably hundreds of genes that can cause myopia, and so far, only 25 candidates have been identified. The high-risk variant of APLP2 is relatively uncommon, occurring in about 1 percent of the population.

Though a drug or gene therapy to prevent myopia may be years away, Dr. Tkatchenko says spending time outdoors is the best way to reduce kids' risk of developing myopia.

"We pretty much know all the environmental risk factors: time spent reading increases the risk, while time spent outdoors reduces it," Dr. Tkatchenko says.

Myopia rates have shot up in recent years due to changes in these environmental factors. In the U.S., 44 percent of adults are now nearsighted, up from 25 percent 30 years ago. And in some parts of Asia, 80 percent of young adults are now myopic.

"The critical period for myopia development is during elementary and middle school, so when kids are in school, make sure they also spend at least two hours outdoors each day," Dr. Tkatchenko says.

Preventing myopia not only reduces the need for vision correction, but also prevents potentially blinding eye conditions later in life.

"People say, 'What's so terrible about myopia? You just have to get glasses,'" Dr. Tkatchenko says, "But myopia increases the risk of developing cataracts, glaucoma, and retinal detachment later in life. All of these can lead to blindness.

"Even in people with mild myopia there is a significant risk, but it's especially high in people who need five or more diopters of vision correction (about 20/400 vision). That's why it's important to study myopia."

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The paper is titled "APLP2 regulates refractive error and myopia development in mice and humans." The authors are: Andrei V. Tkatchenko, Tatiana V. Tkatchenko, Jeremy A. Guggenheim (Cardiff University), Virginie J. M. Verhoeven (Erasmus Medical Center), Pirro G. Hysi (King's College London School of Medicine), Robert Wojciechowski (Johns Hopkins Bloomberg School of Public Health and NIH), Pawan Kumar Singh (Wayne State University), Ashok Kumar (Wayne State University), Gopal Thinakaran (University of Chicago), Consortium for Refractive Error and Myopia, and Cathy Williams (University of Bristol).

The work was supported by the National Eye Institute of NIH (grants R21EY018902 and R01EY023839), research grants from the Midwest Eye-Banks, and the generous donations from the Acquavella Family Foundation and Joseph Connors.

The CUMC investigators report no conflicts of interest.

Columbia University Medical Center provides international leadership in basic, preclinical, and clinical research; medical and health sciences education; and patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Columbia University Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest faculty medical practices in the Northeast. For more information, visit cumc.columbia.edu or columbiadoctors.org.

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