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Bis(monoacylglycero)phosphate lipids in the retinal pigment epithelium implicate lysosomal/endosomal dysfunction in a model of Stargardt disease and human retinas

Stargardt disease is a juvenile onset retinal degeneration, associated with elevated levels of lipofuscin and its bis-retinoid components, such as N-retinylidene-N-retinylethanolamine (A2E). However, the pathogenesis of Stargardt is still poorly understood and targeted treatments are not available....

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Autores principales: Anderson, David M. G., Ablonczy, Zsolt, Koutalos, Yiannis, Hanneken, Anne M., Spraggins, Jeffrey M., Calcutt, M. Wade, Crouch, Rosalie K., Caprioli, Richard M., Schey, Kevin L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725462/
https://www.ncbi.nlm.nih.gov/pubmed/29229934
http://dx.doi.org/10.1038/s41598-017-17402-1
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author Anderson, David M. G.
Ablonczy, Zsolt
Koutalos, Yiannis
Hanneken, Anne M.
Spraggins, Jeffrey M.
Calcutt, M. Wade
Crouch, Rosalie K.
Caprioli, Richard M.
Schey, Kevin L.
author_facet Anderson, David M. G.
Ablonczy, Zsolt
Koutalos, Yiannis
Hanneken, Anne M.
Spraggins, Jeffrey M.
Calcutt, M. Wade
Crouch, Rosalie K.
Caprioli, Richard M.
Schey, Kevin L.
author_sort Anderson, David M. G.
collection PubMed
description Stargardt disease is a juvenile onset retinal degeneration, associated with elevated levels of lipofuscin and its bis-retinoid components, such as N-retinylidene-N-retinylethanolamine (A2E). However, the pathogenesis of Stargardt is still poorly understood and targeted treatments are not available. Utilizing high spatial and high mass resolution matrix assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS), we determined alterations of lipid profiles specifically localized to the retinal pigment epithelium (RPE) in Abca4 (−/−) Stargardt model mice compared to their relevant background strain. Extensive analysis by LC-MS/MS in both positive and negative ion mode was required to accurately confirm the identity of one highly expressed lipid class, bis(monoacylgylercoro)phosphate (BMP) lipids, and to distinguish them from isobaric species. The same BMP lipids were also detected in the RPE of healthy human retina. BMP lipids have been previously associated with the endosomal/lysosomal storage diseases Niemann-Pick and neuronal ceroid lipofuscinosis and have been reported to regulate cholesterol levels in endosomes. These results suggest that perturbations in lipid metabolism associated with late endosomal/lysosomal dysfunction may play a role in the pathogenesis of Stargardt disease and is evidenced in human retinas.
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spelling pubmed-57254622017-12-13 Bis(monoacylglycero)phosphate lipids in the retinal pigment epithelium implicate lysosomal/endosomal dysfunction in a model of Stargardt disease and human retinas Anderson, David M. G. Ablonczy, Zsolt Koutalos, Yiannis Hanneken, Anne M. Spraggins, Jeffrey M. Calcutt, M. Wade Crouch, Rosalie K. Caprioli, Richard M. Schey, Kevin L. Sci Rep Article Stargardt disease is a juvenile onset retinal degeneration, associated with elevated levels of lipofuscin and its bis-retinoid components, such as N-retinylidene-N-retinylethanolamine (A2E). However, the pathogenesis of Stargardt is still poorly understood and targeted treatments are not available. Utilizing high spatial and high mass resolution matrix assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS), we determined alterations of lipid profiles specifically localized to the retinal pigment epithelium (RPE) in Abca4 (−/−) Stargardt model mice compared to their relevant background strain. Extensive analysis by LC-MS/MS in both positive and negative ion mode was required to accurately confirm the identity of one highly expressed lipid class, bis(monoacylgylercoro)phosphate (BMP) lipids, and to distinguish them from isobaric species. The same BMP lipids were also detected in the RPE of healthy human retina. BMP lipids have been previously associated with the endosomal/lysosomal storage diseases Niemann-Pick and neuronal ceroid lipofuscinosis and have been reported to regulate cholesterol levels in endosomes. These results suggest that perturbations in lipid metabolism associated with late endosomal/lysosomal dysfunction may play a role in the pathogenesis of Stargardt disease and is evidenced in human retinas. Nature Publishing Group UK 2017-12-11 /pmc/articles/PMC5725462/ /pubmed/29229934 http://dx.doi.org/10.1038/s41598-017-17402-1 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
Anderson, David M. G.
Ablonczy, Zsolt
Koutalos, Yiannis
Hanneken, Anne M.
Spraggins, Jeffrey M.
Calcutt, M. Wade
Crouch, Rosalie K.
Caprioli, Richard M.
Schey, Kevin L.
Bis(monoacylglycero)phosphate lipids in the retinal pigment epithelium implicate lysosomal/endosomal dysfunction in a model of Stargardt disease and human retinas
title Bis(monoacylglycero)phosphate lipids in the retinal pigment epithelium implicate lysosomal/endosomal dysfunction in a model of Stargardt disease and human retinas
title_full Bis(monoacylglycero)phosphate lipids in the retinal pigment epithelium implicate lysosomal/endosomal dysfunction in a model of Stargardt disease and human retinas
title_fullStr Bis(monoacylglycero)phosphate lipids in the retinal pigment epithelium implicate lysosomal/endosomal dysfunction in a model of Stargardt disease and human retinas
title_full_unstemmed Bis(monoacylglycero)phosphate lipids in the retinal pigment epithelium implicate lysosomal/endosomal dysfunction in a model of Stargardt disease and human retinas
title_short Bis(monoacylglycero)phosphate lipids in the retinal pigment epithelium implicate lysosomal/endosomal dysfunction in a model of Stargardt disease and human retinas
title_sort bis(monoacylglycero)phosphate lipids in the retinal pigment epithelium implicate lysosomal/endosomal dysfunction in a model of stargardt disease and human retinas
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725462/
https://www.ncbi.nlm.nih.gov/pubmed/29229934
http://dx.doi.org/10.1038/s41598-017-17402-1
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