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Please use this identifier to cite or link to this item: http://hdl.handle.net/10481/31033

Title: Sortilin Participates in Light-dependent Photoreceptor Degeneration in Vivo
Authors: Santos Carro, Ana María
López-Sánchez, Noelia
Martín Oliva, David
Villa, Pedro de la
Cuadros Ojeda, Miguel Ángel
Frade, José M.
Issue Date: 2012
Abstract: Both proNGF and the neurotrophin receptor p75 (p75NTR) are known to regulate photoreceptor cell death caused by exposure of albino mice to intense illumination. ProNGF-induced apoptosis requires the participation of sortilin as a necessary p75NTR co-receptor, suggesting that sortilin may participate in the photoreceptor degeneration triggered by intense lighting. We report here that light-exposed albino mice showed sortilin, p75NTR, and proNGF expression in the outer nuclear layer, the retinal layer where photoreceptor cell bodies are located. In addition, cone progenitor-derived 661W cells subjected to intense illumination expressed sortilin and p75NTR and released proNGF into the culture medium. Pharmacological blockade of sortilin with either neurotensin or the “pro” domain of proNGF (pro-peptide) favored the survival of 661W cells subjected to intense light. In vivo, the pro-peptide attenuated retinal cell death in light-exposed albino mice. We propose that an auto/paracrine proapoptotic mechanism based on the interaction of proNGF with the receptor complex p75NTR/sortilin participates in intense light-dependent photoreceptor cell death. We therefore propose sortilin as a putative target for intervention in hereditary retinal dystrophies.
Sponsorship: This study was supported by grants from the “Ministerio de Ciencia e Innovación” (BFU2009-07671) and from “Fundación Lucha contra la Ceguera” (FUNDALUCE-2008) to JMF, as well as from “Ministerio de Ciencia e Innovación” (BFU2007-61659), from “Junta de Andalucia” (P07-CVI-03008), and from “University of Granada” (2011 GREIB incentive) to MAC.
Publisher: Public Library of Science (PLOS)
Keywords: Apoptosis
Cell death
Enzyme-linked immunoassays
Immunohsitochemistry techniques
URI: http://hdl.handle.net/10481/31033
ISSN: 1932-6203
Rights : Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License
Citation: Santos, A.M.; et al. Sortilin Participates in Light-dependent Photoreceptor Degeneration in Vivo. Plos One, 7(4): e36243 (2012). [http://hdl.handle.net/10481/31033]
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