Retinal Degeneration In A Mouse Model Of CLN5 Disease Is Associated With Compromised Autophagy

Abstract The Finnish variant of late infantile neuronal ceroid lipofuscinosis (CLN5 disease) belongs to a family of neuronal ceroid lipofuscinosis (NCLs) diseases. Vision loss is among the first clinical signs in childhood forms of NCLs. Mutations in CLN5 underlie CLN5 disease. The aim of this study...

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Autores principales:	Henri Leinonen, Velta Keksa-Goldsteine, Symantas Ragauskas, Philip Kohlmann, Yajuvinder Singh, Ekaterina Savchenko, Jooseppi Puranen, Tarja Malm, Giedrius Kalesnykas, Jari Koistinaho, Heikki Tanila, Katja M. Kanninen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bb6f6dcb4fdd4a55869968c7e9693326
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spelling	oai:doaj.org-article:bb6f6dcb4fdd4a55869968c7e96933262021-12-02T15:05:38ZRetinal Degeneration In A Mouse Model Of CLN5 Disease Is Associated With Compromised Autophagy10.1038/s41598-017-01716-12045-2322https://doaj.org/article/bb6f6dcb4fdd4a55869968c7e96933262017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01716-1https://doaj.org/toc/2045-2322Abstract The Finnish variant of late infantile neuronal ceroid lipofuscinosis (CLN5 disease) belongs to a family of neuronal ceroid lipofuscinosis (NCLs) diseases. Vision loss is among the first clinical signs in childhood forms of NCLs. Mutations in CLN5 underlie CLN5 disease. The aim of this study was to characterize how the lack of normal functionality of the CLN5 protein affects the mouse retina. Scotopic electroretinography (ERG) showed a diminished c-wave amplitude in the CLN5 deficient mice already at 1 month of age, indicative of pathological events in the retinal pigmented epithelium. A- and b-waves showed progressive impairment later from 2 and 3 months of age onwards, respectively. Structural and immunohistochemical (IHC) analyses showed preferential damage of photoreceptors, accumulation of autofluorescent storage material, apoptosis of photoreceptors, and strong inflammation in the CLN5 deficient mice retinas. Increased levels of autophagy-associated proteins Beclin-1 and P62, and increased LC3b-II/LC3b-I ratio, were detected by Western blotting from whole retinal extracts. Photopic ERG, visual evoked potentials, IHC and cell counting indicated relatively long surviving cone photoreceptors compared to rods. In conclusion, CLN5 deficient mice develop early vision loss that reflects the condition reported in clinical childhood forms of NCLs. The vision loss in CLN5 deficient mice is primarily caused by photoreceptor degeneration.Henri LeinonenVelta Keksa-GoldsteineSymantas RagauskasPhilip KohlmannYajuvinder SinghEkaterina SavchenkoJooseppi PuranenTarja MalmGiedrius KalesnykasJari KoistinahoHeikki TanilaKatja M. KanninenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Henri Leinonen Velta Keksa-Goldsteine Symantas Ragauskas Philip Kohlmann Yajuvinder Singh Ekaterina Savchenko Jooseppi Puranen Tarja Malm Giedrius Kalesnykas Jari Koistinaho Heikki Tanila Katja M. Kanninen Retinal Degeneration In A Mouse Model Of CLN5 Disease Is Associated With Compromised Autophagy
description	Abstract The Finnish variant of late infantile neuronal ceroid lipofuscinosis (CLN5 disease) belongs to a family of neuronal ceroid lipofuscinosis (NCLs) diseases. Vision loss is among the first clinical signs in childhood forms of NCLs. Mutations in CLN5 underlie CLN5 disease. The aim of this study was to characterize how the lack of normal functionality of the CLN5 protein affects the mouse retina. Scotopic electroretinography (ERG) showed a diminished c-wave amplitude in the CLN5 deficient mice already at 1 month of age, indicative of pathological events in the retinal pigmented epithelium. A- and b-waves showed progressive impairment later from 2 and 3 months of age onwards, respectively. Structural and immunohistochemical (IHC) analyses showed preferential damage of photoreceptors, accumulation of autofluorescent storage material, apoptosis of photoreceptors, and strong inflammation in the CLN5 deficient mice retinas. Increased levels of autophagy-associated proteins Beclin-1 and P62, and increased LC3b-II/LC3b-I ratio, were detected by Western blotting from whole retinal extracts. Photopic ERG, visual evoked potentials, IHC and cell counting indicated relatively long surviving cone photoreceptors compared to rods. In conclusion, CLN5 deficient mice develop early vision loss that reflects the condition reported in clinical childhood forms of NCLs. The vision loss in CLN5 deficient mice is primarily caused by photoreceptor degeneration.
format	article
author	Henri Leinonen Velta Keksa-Goldsteine Symantas Ragauskas Philip Kohlmann Yajuvinder Singh Ekaterina Savchenko Jooseppi Puranen Tarja Malm Giedrius Kalesnykas Jari Koistinaho Heikki Tanila Katja M. Kanninen
author_facet	Henri Leinonen Velta Keksa-Goldsteine Symantas Ragauskas Philip Kohlmann Yajuvinder Singh Ekaterina Savchenko Jooseppi Puranen Tarja Malm Giedrius Kalesnykas Jari Koistinaho Heikki Tanila Katja M. Kanninen
author_sort	Henri Leinonen
title	Retinal Degeneration In A Mouse Model Of CLN5 Disease Is Associated With Compromised Autophagy
title_short	Retinal Degeneration In A Mouse Model Of CLN5 Disease Is Associated With Compromised Autophagy
title_full	Retinal Degeneration In A Mouse Model Of CLN5 Disease Is Associated With Compromised Autophagy
title_fullStr	Retinal Degeneration In A Mouse Model Of CLN5 Disease Is Associated With Compromised Autophagy
title_full_unstemmed	Retinal Degeneration In A Mouse Model Of CLN5 Disease Is Associated With Compromised Autophagy
title_sort	retinal degeneration in a mouse model of cln5 disease is associated with compromised autophagy
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/bb6f6dcb4fdd4a55869968c7e9693326
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_version_	1718388789774123008

Retinal Degeneration In A Mouse Model Of CLN5 Disease Is Associated With Compromised Autophagy

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