Photoreceptor-induced RPE phagolysosomal maturation defects in Stargardt-like Maculopathy (STGD3)

Abstract For many neurodegenerative disorders, expression of a pathological protein by one cell type impedes function of other cell types, which in turn contributes to the death of the first cell type. In transgenic mice modelling Stargardt-like (STGD3) maculopathy, human mutant ELOVL4 expression by...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Camille Dejos, Sharee Kuny, Woo Hyun Han, Heather Capel, Hélène Lemieux, Yves Sauvé
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a678339708ca45858f64f495a3c5912a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a678339708ca45858f64f495a3c5912a
record_format	dspace
spelling	oai:doaj.org-article:a678339708ca45858f64f495a3c5912a2021-12-02T15:08:41ZPhotoreceptor-induced RPE phagolysosomal maturation defects in Stargardt-like Maculopathy (STGD3)10.1038/s41598-018-24357-42045-2322https://doaj.org/article/a678339708ca45858f64f495a3c5912a2018-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-24357-4https://doaj.org/toc/2045-2322Abstract For many neurodegenerative disorders, expression of a pathological protein by one cell type impedes function of other cell types, which in turn contributes to the death of the first cell type. In transgenic mice modelling Stargardt-like (STGD3) maculopathy, human mutant ELOVL4 expression by photoreceptors is associated with defects in the underlying retinal pigment epithelium (RPE). To examine how photoreceptors exert cytotoxic effects on RPE cells, transgenic ELOVL4 (TG1–2 line; TG) and wild-type (WT) littermates were studied one month prior (preclinical stage) to onset of photoreceptor loss (two months). TG photoreceptor outer segments presented to human RPE cells are recognized and internalized into phagosomes, but their digestion is delayed. Live RPE cell imaging pinpoints decreased numbers of acidified phagolysomes. In vivo, master regulator of lysosomal genes, transcription factor EB (TFEB), and key lysosomal enzyme Cathepsin D are both unaffected. Oxidative stress, as ruled out with high-resolution respirometry, does not play a role at such an early stage. Upregulation of CRYBA1/A3 and phagocytic cells (microglia/macrophages) interposed between RPE and photoreceptors support adaptive responses to processing delays. Impaired phagolysosomal maturation is observed in RPE of mice expressing human mutant ELOVL4 in their photoreceptors prior to photoreceptor death and associated vision loss.Camille DejosSharee KunyWoo Hyun HanHeather CapelHélène LemieuxYves SauvéNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-14 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Camille Dejos Sharee Kuny Woo Hyun Han Heather Capel Hélène Lemieux Yves Sauvé Photoreceptor-induced RPE phagolysosomal maturation defects in Stargardt-like Maculopathy (STGD3)
description	Abstract For many neurodegenerative disorders, expression of a pathological protein by one cell type impedes function of other cell types, which in turn contributes to the death of the first cell type. In transgenic mice modelling Stargardt-like (STGD3) maculopathy, human mutant ELOVL4 expression by photoreceptors is associated with defects in the underlying retinal pigment epithelium (RPE). To examine how photoreceptors exert cytotoxic effects on RPE cells, transgenic ELOVL4 (TG1–2 line; TG) and wild-type (WT) littermates were studied one month prior (preclinical stage) to onset of photoreceptor loss (two months). TG photoreceptor outer segments presented to human RPE cells are recognized and internalized into phagosomes, but their digestion is delayed. Live RPE cell imaging pinpoints decreased numbers of acidified phagolysomes. In vivo, master regulator of lysosomal genes, transcription factor EB (TFEB), and key lysosomal enzyme Cathepsin D are both unaffected. Oxidative stress, as ruled out with high-resolution respirometry, does not play a role at such an early stage. Upregulation of CRYBA1/A3 and phagocytic cells (microglia/macrophages) interposed between RPE and photoreceptors support adaptive responses to processing delays. Impaired phagolysosomal maturation is observed in RPE of mice expressing human mutant ELOVL4 in their photoreceptors prior to photoreceptor death and associated vision loss.
format	article
author	Camille Dejos Sharee Kuny Woo Hyun Han Heather Capel Hélène Lemieux Yves Sauvé
author_facet	Camille Dejos Sharee Kuny Woo Hyun Han Heather Capel Hélène Lemieux Yves Sauvé
author_sort	Camille Dejos
title	Photoreceptor-induced RPE phagolysosomal maturation defects in Stargardt-like Maculopathy (STGD3)
title_short	Photoreceptor-induced RPE phagolysosomal maturation defects in Stargardt-like Maculopathy (STGD3)
title_full	Photoreceptor-induced RPE phagolysosomal maturation defects in Stargardt-like Maculopathy (STGD3)
title_fullStr	Photoreceptor-induced RPE phagolysosomal maturation defects in Stargardt-like Maculopathy (STGD3)
title_full_unstemmed	Photoreceptor-induced RPE phagolysosomal maturation defects in Stargardt-like Maculopathy (STGD3)
title_sort	photoreceptor-induced rpe phagolysosomal maturation defects in stargardt-like maculopathy (stgd3)
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/a678339708ca45858f64f495a3c5912a
work_keys_str_mv	AT camilledejos photoreceptorinducedrpephagolysosomalmaturationdefectsinstargardtlikemaculopathystgd3 AT shareekuny photoreceptorinducedrpephagolysosomalmaturationdefectsinstargardtlikemaculopathystgd3 AT woohyunhan photoreceptorinducedrpephagolysosomalmaturationdefectsinstargardtlikemaculopathystgd3 AT heathercapel photoreceptorinducedrpephagolysosomalmaturationdefectsinstargardtlikemaculopathystgd3 AT helenelemieux photoreceptorinducedrpephagolysosomalmaturationdefectsinstargardtlikemaculopathystgd3 AT yvessauve photoreceptorinducedrpephagolysosomalmaturationdefectsinstargardtlikemaculopathystgd3
_version_	1718388079530606592

Photoreceptor-induced RPE phagolysosomal maturation defects in Stargardt-like Maculopathy (STGD3)

Ejemplares similares