Sfrp1 deficiency makes retinal photoreceptors prone to degeneration

Abstract 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 un...

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Autores principales:	Elsa Cisneros, Fabiana di Marco, Javier Rueda-Carrasco, Concepción Lillo, Guadalupe Pereyra, María Jesús Martín-Bermejo, Alba Vargas, Rocío Sanchez, África Sandonís, Pilar Esteve, Paola Bovolenta
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4af7a7b0c20345daadb50c8fd64c75f4
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spelling	oai:doaj.org-article:4af7a7b0c20345daadb50c8fd64c75f42021-12-02T16:30:58ZSfrp1 deficiency makes retinal photoreceptors prone to degeneration10.1038/s41598-020-61970-82045-2322https://doaj.org/article/4af7a7b0c20345daadb50c8fd64c75f42020-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-61970-8https://doaj.org/toc/2045-2322Abstract 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.Elsa CisnerosFabiana di MarcoJavier Rueda-CarrascoConcepción LilloGuadalupe PereyraMaría Jesús Martín-BermejoAlba VargasRocío SanchezÁfrica SandonísPilar EstevePaola BovolentaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-16 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Elsa Cisneros Fabiana di Marco Javier Rueda-Carrasco Concepción Lillo Guadalupe Pereyra María Jesús Martín-Bermejo Alba Vargas Rocío Sanchez África Sandonís Pilar Esteve Paola Bovolenta Sfrp1 deficiency makes retinal photoreceptors prone to degeneration
description	Abstract 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.
format	article
author	Elsa Cisneros Fabiana di Marco Javier Rueda-Carrasco Concepción Lillo Guadalupe Pereyra María Jesús Martín-Bermejo Alba Vargas Rocío Sanchez África Sandonís Pilar Esteve Paola Bovolenta
author_facet	Elsa Cisneros Fabiana di Marco Javier Rueda-Carrasco Concepción Lillo Guadalupe Pereyra María Jesús Martín-Bermejo Alba Vargas Rocío Sanchez África Sandonís Pilar Esteve Paola Bovolenta
author_sort	Elsa Cisneros
title	Sfrp1 deficiency makes retinal photoreceptors prone to degeneration
title_short	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_sort	sfrp1 deficiency makes retinal photoreceptors prone to degeneration
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/4af7a7b0c20345daadb50c8fd64c75f4
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Sfrp1 deficiency makes retinal photoreceptors prone to degeneration

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