Transcriptome-based insights into gene networks controlling myopia prevention

dc.contributor.authorKarouta, Cindy
dc.contributor.authorKucharski, Robert
dc.contributor.authorHardy, Kristine
dc.contributor.authorThomson, Kate
dc.contributor.authorMaleszka, Ryszard
dc.contributor.authorMorgan, Ian
dc.contributor.authorAshby, Regan
dc.date.accessioned2022-11-13T22:35:26Z
dc.date.available2022-11-13T22:35:26Z
dc.date.issued2021
dc.date.updated2024-03-03T07:16:41Z
dc.description.abstractMyopia (short-sightedness), usually caused by excessive elongation of the eye during development, has reached epidemic proportions worldwide. In animal systems including the chicken model, several treatments have been shown to inhibit ocular elongation and experimental myopia. Although diverse in their apparent mechanism of action, each one leads to a reduction in the rate of ocular growth. We hypothesize that a defined set of retinal molecular changes may underlie growth inhibition, irrespective of the treatment agent used. Accordingly, across five well-established but diverse methods of inhibiting myopia, significant overlap is seen in the retinal transcriptome profile (transcript levels and alternative splicing events) in chicks when analyzed by RNA-seq. Within the two major pathway networks enriched during growth inhibition, that of cell signaling and circadian entrainment, transcription factors form the largest functional grouping. Importantly, a large percentage of those genes forming the defined retinal response are downstream targets of the transcription factor EGR1 which itself shows a universal response to all five growth-inhibitory treatments. This supports EGR1's previously implicated role in ocular growth regulation. Finally, by contrasting our data with human linkage and GWAS studies on refractive error, we confirm the applicability of our study to the human condition. Together, these findings suggest that a universal set of transcriptome changes, which sit within a well-defined retinal network that cannot be bypassed, is fundamental to growth regulation, thus paving a way for designing novel targets for myopia therapies.
dc.description.sponsorshipThis work was partially funded by ANU Connect Ventures through a Discovery Translation Fund (Project number DTF311) and was awarded to RA.en_AU
dc.format.mimetypeapplication/pdfen_AU
dc.identifier.issn0892-6638en_AU
dc.identifier.urihttp://hdl.handle.net/1885/278801
dc.language.isoen_AUen_AU
dc.provenanceThis is an open access article under the terms of the Creative Commons Attri bution- NonCommercial- NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.en_AU
dc.publisherFederation of American Societies for Experimental Biology
dc.rights© 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology
dc.rights.licenseCreative Commons Attri bution- NonCommercial- NoDerivs Licenseen_AU
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en_AU
dc.sourceFASEB Journal
dc.subjectgene expression
dc.subjectmyopia
dc.subjectretina
dc.subjectRNA sequencing
dc.subjecttranscriptome
dc.titleTranscriptome-based insights into gene networks controlling myopia prevention
dc.typeJournal article
dcterms.accessRightsOpen Accessen_AU
local.bibliographicCitation.issue9en_AU
local.bibliographicCitation.lastpage23en_AU
local.bibliographicCitation.startpage1en_AU
local.contributor.affiliationKarouta, Cindy, University of Canberraen_AU
local.contributor.affiliationKucharski, Robert, College of Science, ANUen_AU
local.contributor.affiliationHardy, Kristine, University of Canberraen_AU
local.contributor.affiliationThomson, Kate, University of Canberraen_AU
local.contributor.affiliationMaleszka, Ryszard, College of Science, ANUen_AU
local.contributor.affiliationMorgan, Ian, College of Science, ANUen_AU
local.contributor.affiliationAshby, Regan, College of Science, ANUen_AU
local.contributor.authoremailu8709305@anu.edu.auen_AU
local.contributor.authoruidKucharski, Robert, u9612185en_AU
local.contributor.authoruidMaleszka, Ryszard, u8709305en_AU
local.contributor.authoruidMorgan, Ian, u7401805en_AU
local.contributor.authoruidAshby, Regan, u2532493en_AU
local.description.notesImported from ARIESen_AU
local.identifier.absfor321204 - Vision scienceen_AU
local.identifier.absfor310505 - Gene expression (incl. microarray and other genome-wide approaches)en_AU
local.identifier.absfor321201 - Ophthalmologyen_AU
local.identifier.absseo280102 - Expanding knowledge in the biological sciencesen_AU
local.identifier.absseo280112 - Expanding knowledge in the health sciencesen_AU
local.identifier.absseo209999 - Other health not elsewhere classifieden_AU
local.identifier.ariespublicationa383154xPUB22063en_AU
local.identifier.citationvolume35en_AU
local.identifier.doi10.1096/fj.202100350RRen_AU
local.identifier.scopusID2-s2.0-85113585930
local.identifier.thomsonIDWOS:000691122900007
local.identifier.uidSubmittedBya383154en_AU
local.publisher.urlhttps://www.wiley.com/en-gben_AU
local.type.statusPublished Versionen_AU

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