BioSpace - Sortilin Participates in Light-dependent Photoreceptor Degeneration in Vivo

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PLoS By Category | Recent PLoS Articles

Biochemistry - Neuroscience - Ophthalmology

Sortilin Participates in Light-dependent Photoreceptor Degeneration in Vivo
Published: Friday, April 27, 2012
Author: Ana M. Santos et al.

by Ana M. Santos, Noelia López-Sánchez, David Martín-Oliva, Pedro de la Villa, Miguel A. Cuadros, José M. Frade

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 hereditary retinal dystrophies. More...