Deletion of IFT20 exclusively in the RPE ablates primary cilia and leads to retinal degeneration

dc.contributor.authorKretschmer, Viola
dc.contributor.authorSchneider, Sandra
dc.contributor.authorMatthiessen, Peter Andreas
dc.contributor.authorReichert, Dominik
dc.contributor.authorHotaling, Nathan
dc.contributor.authorGlasßer, Gunnar
dc.contributor.authorLieberwirth, Ingo
dc.contributor.authorBharti, Kapil
dc.contributor.authorDe Cegli, Rossella
dc.contributor.authorConte, Ivan
dc.contributor.authorNandrot, Emeline F.
dc.contributor.authorMay-Simera, Helen Louise
dc.date.accessioned2024-02-06T15:36:26Z
dc.date.available2024-02-06T15:36:26Z
dc.date.issued2023
dc.description.abstractVision impairment places a serious burden on the aging society, affecting the lives of millions of people. Many retinal diseases are of genetic origin, of which over 50% are due to mutations in cilia-associated genes. Most research on retinal degeneration has focused on the ciliated photoreceptor cells of the retina. However, the contribution of primary cilia in other ocular cell types has largely been ignored. The retinal pigment epithelium (RPE) is a monolayer epithelium at the back of the eye intricately associated with photoreceptors and essential for visual function. It is already known that primary cilia in the RPE are critical for its development and maturation; however, it remains unclear whether this affects RPE function and retinal tissue homeostasis. We generated a conditional knockout mouse model, in which IFT20 is exclusively deleted in the RPE, ablating primary cilia. This leads to defective RPE function, followed by photoreceptor degeneration and, ultimately, vision impairment. Transcriptomic analysis offers insights into mechanisms underlying pathogenic changes, which include transcripts related to epithelial homeostasis, the visual cycle, and phagocytosis. Due to the loss of cilia exclusively in the RPE, this mouse model enables us to tease out the functional role of RPE cilia and their contribution to retinal degeneration, providing a powerful tool for basic and translational research in syndromic and non-syndromic retinal degeneration. Non-ciliary mechanisms of IFT20 in the RPE may also contribute to pathogenesis and cannot be excluded, especially considering the increasing evidence of non-ciliary functions of ciliary proteins.en_GB
dc.identifier.doihttp://doi.org/10.25358/openscience-9983
dc.identifier.urihttps://openscience.ub.uni-mainz.de/handle/20.500.12030/10001
dc.language.isoengde
dc.rightsCC-BY-4.0*
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.subject.ddc570 Biowissenschaftende_DE
dc.subject.ddc570 Life sciencesen_GB
dc.titleDeletion of IFT20 exclusively in the RPE ablates primary cilia and leads to retinal degenerationen_GB
dc.typeZeitschriftenaufsatzde
jgu.journal.issue12de
jgu.journal.titlePLoS biologyde
jgu.journal.volume21de
jgu.organisation.departmentFB 10 Biologiede
jgu.organisation.nameJohannes Gutenberg-Universität Mainz
jgu.organisation.number7970
jgu.organisation.placeMainz
jgu.organisation.rorhttps://ror.org/023b0x485
jgu.pages.alternativee3002402de
jgu.publisher.doi10.1371/journal.pbio.3002402de
jgu.publisher.issn1545-7885de
jgu.publisher.namePublic Library of Sciencede
jgu.publisher.placeLawrence, KSde
jgu.publisher.year2023
jgu.rights.accessrightsopenAccess
jgu.subject.ddccode570de
jgu.subject.dfgLebenswissenschaftende
jgu.type.contenttypeScientific articlede
jgu.type.dinitypeArticleen_GB
jgu.type.resourceTextde
jgu.type.versionPublished versionde

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