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Sfrp1 deficiency makes retinal photoreceptors prone to degeneration

Cisneros, E; di Marco, F; Rueda-Carrasco, J; Lillo, C; Pereyra, G; Martín-Bermejo, MJ; Vargas, A; ... Bovolenta, P; + view all (2020) Sfrp1 deficiency makes retinal photoreceptors prone to degeneration. Scientific Reports , 10 (1) , Article 5115. 10.1038/s41598-020-61970-8. Green open access

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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 Rpe6^{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.

Type: Article
Title: Sfrp1 deficiency makes retinal photoreceptors prone to degeneration
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41598-020-61970-8
Publisher version: https://doi.org/10.1038/s41598-020-61970-8
Language: English
Additional information: © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).
Keywords: Cellular neuroscience, Retinal diseases
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > UK Dementia Research Institute
URI: https://discovery.ucl.ac.uk/id/eprint/10094488
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