Authors:	Kretschmer, Viola Schneider, Sandra Matthiessen, Peter Andreas Reichert, Dominik Hotaling, Nathan Glasßer, Gunnar Lieberwirth, Ingo Bharti, Kapil De Cegli, Rossella Conte, Ivan Nandrot, Emeline F. May-Simera, Helen Louise
Title:	Deletion of IFT20 exclusively in the RPE ablates primary cilia and leads to retinal degeneration
Online publication date:	6-Feb-2024
Year of first publication:	2023
Language:	english
Abstract:	Vision 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.
DDC:	570 Biowissenschaften 570 Life sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 10 Biologie
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-9983
Version:	Published version
Publication type:	Zeitschriftenaufsatz
Document type specification:	Scientific article
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/4.0/
Journal:	PLoS biology 2023
Pages or article number:	3002402
Publisher:	Public Library of Science
Publisher place:	Lawrence, KS
Issue date:	2023
ISSN:	1545-7885
Publisher DOI:	10.1371/journal.pbio.3002402
Appears in collections:	DFG-491381577-G