Troilo, Benavente-Pérez: Gene Changes Driving Myopia Reveal New Focus for Drug Development

Dr. David Troilo
 Dr. David Troilo

Myopia (nearsightedness) and hyperopia (farsightedness) develop through different molecular pathways, according to a study published October 9 in the open-access journal PLOS Biology by SUNY Optometry’s Dr. David Troilo and Dr. Alexandra Benavente-Pérez and collaborators at Columbia University. The finding provides a new understanding of eye growth and the development of myopia, the most common form of visual impairment worldwide, and opens the way for the development of new treatments and drugs to prevent it. “Identification of these pathways provides a framework for the identification of new drug targets and for the development of more effective treatment options for myopia,” said Dr. Troilo, who is also the College’s dean and vice president for academic affairs.

Myopia is expected to affect nearly half the world’s population in the next three decades; reducing its progression is a public health priority. The condition occurs when the eye grows too long, increasing the distance between lens and retina such that the image produced by the eye comes into focus at a point in front of, rather than on, the retina. In hyperopia, the opposite occurs; the eye is too short, and the focal point is behind the retina. Research has shown that these defocus signals alter the rate of eye growth, and things occasionally go wrong resulting in myopia.

The cellular signaling pathways controlling eye growth are not well understood, however, and may be the key to understanding myopia development. To explore those pathways, the authors experimentally induced either myopia or hyperopia using lenses to shift the focal point to behind the retina (“hyperopic defocus”) or in front of the retina (“myopic defocus”). In each case, the eye changes shape, elongating or shortening, to compensate by moving the retina closer to the focal point.

The activity of genes in the retinas exposed to different defocus conditions changed compared to the non-exposed retina (used as a control). The molecular pathways affected, however, were for the most part different between the two types of defocus. While both types of defocus induced changes in cellular signaling pathways, with the scores of genes affected in each case, only a handful were affected by both types of defocus. There were also differences in gene activity over time in each type.

The authors found that 29 of the genes whose activity changed in response to defocus were localized within certain chromosomes (quantitative trait loci) previously found to be associated with human myopia in large-scale genetic studies, suggesting that variations in the expression of genes involved in the normal regulation of eye shape in response to defocus contribute to the development of nearsightedness.

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