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Gene expression in response to optical defocus of opposite signs reveals bidirectional mechanism of visually guided eye growth

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...

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Autores principales: Tkatchenko, Tatiana V., Troilo, David, Benavente-Perez, Alexandra, Tkatchenko, Andrei V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6177118/
https://www.ncbi.nlm.nih.gov/pubmed/30300342
http://dx.doi.org/10.1371/journal.pbio.2006021
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author Tkatchenko, Tatiana V.
Troilo, David
Benavente-Perez, Alexandra
Tkatchenko, Andrei V.
author_facet Tkatchenko, Tatiana V.
Troilo, David
Benavente-Perez, Alexandra
Tkatchenko, Andrei V.
author_sort Tkatchenko, Tatiana V.
collection PubMed
description 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.
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spelling pubmed-61771182018-10-19 Gene expression in response to optical defocus of opposite signs reveals bidirectional mechanism of visually guided eye growth Tkatchenko, Tatiana V. Troilo, David Benavente-Perez, Alexandra Tkatchenko, Andrei V. PLoS Biol Methods and Resources 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. Public Library of Science 2018-10-09 /pmc/articles/PMC6177118/ /pubmed/30300342 http://dx.doi.org/10.1371/journal.pbio.2006021 Text en © 2018 Tkatchenko et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Methods and Resources
Tkatchenko, Tatiana V.
Troilo, David
Benavente-Perez, Alexandra
Tkatchenko, Andrei V.
Gene expression in response to optical defocus of opposite signs reveals bidirectional mechanism of visually guided eye growth
title Gene expression in response to optical defocus of opposite signs reveals bidirectional mechanism of visually guided eye growth
title_full Gene expression in response to optical defocus of opposite signs reveals bidirectional mechanism of visually guided eye growth
title_fullStr Gene expression in response to optical defocus of opposite signs reveals bidirectional mechanism of visually guided eye growth
title_full_unstemmed Gene expression in response to optical defocus of opposite signs reveals bidirectional mechanism of visually guided eye growth
title_short Gene expression in response to optical defocus of opposite signs reveals bidirectional mechanism of visually guided eye growth
title_sort gene expression in response to optical defocus of opposite signs reveals bidirectional mechanism of visually guided eye growth
topic Methods and Resources
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6177118/
https://www.ncbi.nlm.nih.gov/pubmed/30300342
http://dx.doi.org/10.1371/journal.pbio.2006021
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