Cargando…
Retinal Degeneration In A Mouse Model Of CLN5 Disease Is Associated With Compromised Autophagy
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 c...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5431647/ https://www.ncbi.nlm.nih.gov/pubmed/28487519 http://dx.doi.org/10.1038/s41598-017-01716-1 |
_version_ | 1783236469391884288 |
---|---|
author | Leinonen, Henri Keksa-Goldsteine, Velta Ragauskas, Symantas Kohlmann, Philip Singh, Yajuvinder Savchenko, Ekaterina Puranen, Jooseppi Malm, Tarja Kalesnykas, Giedrius Koistinaho, Jari Tanila, Heikki Kanninen, Katja M. |
author_facet | Leinonen, Henri Keksa-Goldsteine, Velta Ragauskas, Symantas Kohlmann, Philip Singh, Yajuvinder Savchenko, Ekaterina Puranen, Jooseppi Malm, Tarja Kalesnykas, Giedrius Koistinaho, Jari Tanila, Heikki Kanninen, Katja M. |
author_sort | Leinonen, Henri |
collection | PubMed |
description | 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 | Online Article Text |
id | pubmed-5431647 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-54316472017-05-16 Retinal Degeneration In A Mouse Model Of CLN5 Disease Is Associated With Compromised Autophagy Leinonen, Henri Keksa-Goldsteine, Velta Ragauskas, Symantas Kohlmann, Philip Singh, Yajuvinder Savchenko, Ekaterina Puranen, Jooseppi Malm, Tarja Kalesnykas, Giedrius Koistinaho, Jari Tanila, Heikki Kanninen, Katja M. Sci Rep Article 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. Nature Publishing Group UK 2017-05-09 /pmc/articles/PMC5431647/ /pubmed/28487519 http://dx.doi.org/10.1038/s41598-017-01716-1 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Leinonen, Henri Keksa-Goldsteine, Velta Ragauskas, Symantas Kohlmann, Philip Singh, Yajuvinder Savchenko, Ekaterina Puranen, Jooseppi Malm, Tarja Kalesnykas, Giedrius Koistinaho, Jari Tanila, Heikki Kanninen, Katja M. Retinal Degeneration In A Mouse Model Of CLN5 Disease Is Associated With Compromised Autophagy |
title | 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_short | 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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5431647/ https://www.ncbi.nlm.nih.gov/pubmed/28487519 http://dx.doi.org/10.1038/s41598-017-01716-1 |
work_keys_str_mv | AT leinonenhenri retinaldegenerationinamousemodelofcln5diseaseisassociatedwithcompromisedautophagy AT keksagoldsteinevelta retinaldegenerationinamousemodelofcln5diseaseisassociatedwithcompromisedautophagy AT ragauskassymantas retinaldegenerationinamousemodelofcln5diseaseisassociatedwithcompromisedautophagy AT kohlmannphilip retinaldegenerationinamousemodelofcln5diseaseisassociatedwithcompromisedautophagy AT singhyajuvinder retinaldegenerationinamousemodelofcln5diseaseisassociatedwithcompromisedautophagy AT savchenkoekaterina retinaldegenerationinamousemodelofcln5diseaseisassociatedwithcompromisedautophagy AT puranenjooseppi retinaldegenerationinamousemodelofcln5diseaseisassociatedwithcompromisedautophagy AT malmtarja retinaldegenerationinamousemodelofcln5diseaseisassociatedwithcompromisedautophagy AT kalesnykasgiedrius retinaldegenerationinamousemodelofcln5diseaseisassociatedwithcompromisedautophagy AT koistinahojari retinaldegenerationinamousemodelofcln5diseaseisassociatedwithcompromisedautophagy AT tanilaheikki retinaldegenerationinamousemodelofcln5diseaseisassociatedwithcompromisedautophagy AT kanninenkatjam retinaldegenerationinamousemodelofcln5diseaseisassociatedwithcompromisedautophagy |