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Sfrp1 deficiency makes retinal photoreceptors prone to degeneration

Millions of individuals worldwide suffer from impaired vision, a condition with multiple origins that often impinge upon the light sensing cells of the retina, the photoreceptors, affecting their integrity. The molecular components contributing to this integrity are however not yet fully understood....

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Autores principales: Cisneros, Elsa, di Marco, Fabiana, Rueda-Carrasco, Javier, Lillo, Concepción, Pereyra, Guadalupe, Martín-Bermejo, María Jesús, Vargas, Alba, Sanchez, Rocío, Sandonís, África, Esteve, Pilar, Bovolenta, Paola
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083943/
https://www.ncbi.nlm.nih.gov/pubmed/32198470
http://dx.doi.org/10.1038/s41598-020-61970-8
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author Cisneros, Elsa
di Marco, Fabiana
Rueda-Carrasco, Javier
Lillo, Concepción
Pereyra, Guadalupe
Martín-Bermejo, María Jesús
Vargas, Alba
Sanchez, Rocío
Sandonís, África
Esteve, Pilar
Bovolenta, Paola
author_facet Cisneros, Elsa
di Marco, Fabiana
Rueda-Carrasco, Javier
Lillo, Concepción
Pereyra, Guadalupe
Martín-Bermejo, María Jesús
Vargas, Alba
Sanchez, Rocío
Sandonís, África
Esteve, Pilar
Bovolenta, Paola
author_sort Cisneros, Elsa
collection PubMed
description Millions of individuals worldwide suffer from impaired vision, a condition with multiple origins that often impinge upon the light sensing cells of the retina, the photoreceptors, affecting their integrity. The molecular components contributing to this integrity are however not yet fully understood. Here we have asked whether Secreted Frizzled Related Protein 1 (SFRP1) may be one of such factors. SFRP1 has a context-dependent function as modulator of Wnt signalling or of the proteolytic activity of A Disintegrin And Metalloproteases (ADAM) 10, a main regulator of neural cell-cell communication. We report that in Sfrp1(−/−) mice, the outer limiting membrane (OLM) is discontinuous and the photoreceptors disorganized and more prone to light-induced damage. Sfrp1 loss significantly enhances the effect of the Rpe65(Leu450Leu) genetic variant -present in the mouse genetic background- which confers sensitivity to light-induced stress. These alterations worsen with age, affect visual function and are associated to an increased proteolysis of Protocadherin 21 (PCDH21), localized at the photoreceptor outer segment, and N-cadherin, an OLM component. We thus propose that SFRP1 contributes to photoreceptor fitness with a mechanism that involves the maintenance of OLM integrity. These conclusions are discussed in view of the broader implication of SFRP1 in neurodegeneration and aging.
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spelling pubmed-70839432020-03-26 Sfrp1 deficiency makes retinal photoreceptors prone to degeneration Cisneros, Elsa di Marco, Fabiana Rueda-Carrasco, Javier Lillo, Concepción Pereyra, Guadalupe Martín-Bermejo, María Jesús Vargas, Alba Sanchez, Rocío Sandonís, África Esteve, Pilar Bovolenta, Paola Sci Rep Article Millions of individuals worldwide suffer from impaired vision, a condition with multiple origins that often impinge upon the light sensing cells of the retina, the photoreceptors, affecting their integrity. The molecular components contributing to this integrity are however not yet fully understood. Here we have asked whether Secreted Frizzled Related Protein 1 (SFRP1) may be one of such factors. SFRP1 has a context-dependent function as modulator of Wnt signalling or of the proteolytic activity of A Disintegrin And Metalloproteases (ADAM) 10, a main regulator of neural cell-cell communication. We report that in Sfrp1(−/−) mice, the outer limiting membrane (OLM) is discontinuous and the photoreceptors disorganized and more prone to light-induced damage. Sfrp1 loss significantly enhances the effect of the Rpe65(Leu450Leu) genetic variant -present in the mouse genetic background- which confers sensitivity to light-induced stress. These alterations worsen with age, affect visual function and are associated to an increased proteolysis of Protocadherin 21 (PCDH21), localized at the photoreceptor outer segment, and N-cadherin, an OLM component. We thus propose that SFRP1 contributes to photoreceptor fitness with a mechanism that involves the maintenance of OLM integrity. These conclusions are discussed in view of the broader implication of SFRP1 in neurodegeneration and aging. Nature Publishing Group UK 2020-03-20 /pmc/articles/PMC7083943/ /pubmed/32198470 http://dx.doi.org/10.1038/s41598-020-61970-8 Text en © The Author(s) 2020 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
Cisneros, Elsa
di Marco, Fabiana
Rueda-Carrasco, Javier
Lillo, Concepción
Pereyra, Guadalupe
Martín-Bermejo, María Jesús
Vargas, Alba
Sanchez, Rocío
Sandonís, África
Esteve, Pilar
Bovolenta, Paola
Sfrp1 deficiency makes retinal photoreceptors prone to degeneration
title Sfrp1 deficiency makes retinal photoreceptors prone to degeneration
title_full Sfrp1 deficiency makes retinal photoreceptors prone to degeneration
title_fullStr Sfrp1 deficiency makes retinal photoreceptors prone to degeneration
title_full_unstemmed Sfrp1 deficiency makes retinal photoreceptors prone to degeneration
title_short Sfrp1 deficiency makes retinal photoreceptors prone to degeneration
title_sort sfrp1 deficiency makes retinal photoreceptors prone to degeneration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083943/
https://www.ncbi.nlm.nih.gov/pubmed/32198470
http://dx.doi.org/10.1038/s41598-020-61970-8
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