Sortilin participates in light-dependent photoreceptor degeneration in vivo.

PloS One
Ana M SantosJosé M Frade

Abstract

Both proNGF and the neurotrophin receptor p75 (p75(NTR)) 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 p75(NTR) 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, p75(NTR), 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 p75(NTR) 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 p75(NTR)/sortilin participates in intense light-dependent photoreceptor cell death. We therefore propose sortilin as a putative target for intervention in heredi...Continue Reading

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Citations

Nov 15, 2013·Journal of Neuroinflammation·Weiyong ShenMark C Gillies
Jun 2, 2015·Molecular Therapy. Methods & Clinical Development·Ahmed Y ShanabAzza B El-Remessy
Dec 15, 2016·Cytokine & Growth Factor Reviews·Tarcyane Barata GarciaAndreas Bringmann
Dec 8, 2016·Experimental Eye Research·Wan-Ju ChenElia J Duh
Jan 1, 2013·Cells·Christelle DevaderJean Mazella
May 31, 2020·Molecular Neurobiology·Giulia MontiOlav M Andersen
May 15, 2019·International Journal of Molecular Sciences·Chao-Wen LinChang-Hao Yang

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Methods Mentioned

BETA
enzyme-linked immunosorbent assay
ELISA
transgenic
electrophoresis
Protein Assay

Software Mentioned

ImageJ

Related Concepts

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis