Abstract

Myopia (nearsightedness) is the most common eye disorder, which is rapidly becoming one of the leading causes of vision loss in several parts of the world because of a recent sharp increase in prevalence. Nearwork, which produces hyperopic optical defocus on the retina, has been implicated as one of the environmental risk factors causing myopia in humans. Experimental studies have shown that hyperopic defocus imposed by negative power lenses placed in front of the eye accelerates eye growth and causes myopia, whereas myopic defocus imposed by positive lenses slows eye growth and produces a compensatory hyperopic shift in refractive state. The balance between these two optical signals is thought to regulate refractive eye development; however, the ability of the retina to recognize the sign of optical defocus and the composition of molecular signaling pathways guiding emmetropization are the subjects of intense investigation and debate. We found that the retina can readily distinguish between imposed myopic and hyperopic defocus, and identified key signaling pathways underlying retinal response to the defocus of different signs. Comparison of retinal transcriptomes in common marmosets exposed to either myopic or hyperopic defocus for 10 days or 5 weeks revealed that the primate retina responds to defocus of different signs by activation or suppression of largely distinct pathways. We also found that 29 genes differentially expressed in the marmoset retina in response to imposed defocus are localized within human myopia quantitative trait loci (QTLs), suggesting functional overlap between genes differentially expressed in the marmoset retina upon exposure to optical defocus and genes causing myopia in humans. These findings identify retinal pathways involved in the development of myopia, as well as potential new strategies for its treatment.

Highlights

  • Core Support for Vision Research received by the Department of Ophthalmology, Columbia University

  • Myopia is an eye disorder characterized by blurred distance vision caused by negative refractive errors when the eye grows too long for its optical power

  • The axial length of the eye grows to match its optical power, producing focused images on the retina; a mismatch between the optical power of the eye and its axial length leads to the development of hyperopia if eyes are too short for their optical power or myopia if eyes grow too long for their optical power

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Summary

Introduction

Myopia (nearsightedness) is an eye disorder characterized by blurred distance vision caused by negative refractive errors when the eye grows too long for its optical power. It is widespread [1], and the prevalence has been increasing around the world at an alarming rate, reaching 80%–90% in several parts of Asia [2,3,4,5]. Imposing myopic defocus on the retina with positive lenses, on the other hand, inhibits eye growth and produces a compensatory hyperopic shift in refraction in fish [28], chickens [21,23], and several mammalian species, including primates [13,16,18,20,25,26].

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