Eyeworld

EW NEWS & OPINION 48 April 2016 by Maxine Lipner EyeWorld Senior Contributing Writer no APLP2, dubbed the knockout version, some had 1 copy of APLP2, known as the heterozygous type, and some, the wild type mice, had 2 copies. "When we looked at refrac- tive eye development, we found that there was no difference between the wild type mice and the heterozygote mice, but the knockout mice, which lacked both copies of APLP2, became highly hyperopic under normal circumstances with no changes in visual environment," Dr. Tkatchenko said. But when investigators induced myopia in these mice, they found a dose-dependent decrease in sus- ceptibility to myopia, depending on whether the mice had 0, 1, or 2 APLP2 copies. Mice with no copies were almost completely protected from myopia, and those with 1 copy were much less susceptible, Dr. Tkatchenko reported, adding that they then looked at the situation much deeper. When they analyzed electrophysiologic properties of the retina, they found that mice with- out APLP2 or with only 1 copy were much less susceptible to changes in contrast and by extension to defocus or degradation of the visual input, he explained. "The less susceptible they were to the changes in contrast, the more protected they became from myopia," Dr. Tkatchenko said, adding that it appears as if those with reduced expression of APLP2 are much less susceptible to the effects of im- age degradation and by extension myopia since this develops when patients are exposed to some sort of degradation of the visual input. The current hypothesis is that in those who have a mutant version of APLP2, the expression of the gene is much higher than in normal children, and therefore they are much more prone to myopia, Dr. Tkatchenko explained. Clinical considerations He views this as a big step forward from a clinical perspective. "It's the first example where we know we can control refractive eye development by modulating expression of a single gene," Dr. Tkatchenko said. "We can theoretically develop some sort of trajectory and how refractive error would change with age in different children depending on whether they carried the normal version of APLP2 or a mutant one. Considering reading They also had data on how many hours each of those children spent reading. "When we separated those children into low readers and high readers, with children who read less than 1 hour a day in 1 group and those who read 1, 2, or 3 hours or more in the other, we noticed that the mutation in APLP2 had no effect on those who read less than 1 hour a day," Dr. Tkatchenko said. "But for those children who read more than 1 hour a day, there was a large difference depending on whether they had the mutant or the normal (gene) version." There was a clear relationship among the version of APLP2 the children had, the visual input, and the amount of time they spent reading, Dr. Tkatchenko noted. He has a theory of what is likely going on here based on work done in a mouse model. "We had a mouse model of myopia, and we looked at how APLP2 influences refractive eye development in the mouse model," he said, adding that some mice had PLoS Genetics, investigators reported that those who carried a mutant version of the APLP2 gene and who were avid readers as children were 5 times as likely to become myopic in their teens as those without this gene. Included in the population- based study was longitudinal information on more than 13,000 children that investigators found from searching a U.K. database. "We had data for refractive error at differ- ent ages," Dr. Tkatchenko said, add- ing that they looked at the refractive Gene leads to nearsightedness for ardent readers A gene has been discov- ered that causes myopia in those who spent a lot of time reading in childhood, according to Andrei Tkatchenko, MD, PhD, associate professor, Department of Ophthalmology, Pathology and Cell Biology, Columbia University, New York. In a recent study 1 published in A deeper look at myopia " We need to be able to identify vulnerable children at an early age, and we need to be able to treat those who are vulnerable so that they won't develop myopia even though they are predisposed to it. " –Andrei Tkatchenko, MD, PhD

• Cover