Referencia

doi:10.1038/cdd.2011.88

Autores

Natalia Rodríguez-Muela, Francisco Germain, Guillermo Mariño, Patrick S Fitze and Patricia Boya.

Resumen

Autophagy is an essential recycling pathway implicated in neurodegeneration either as a pro-survival or a pro-death mechanism. Its role after axonal injury is still uncertain. Axotomy of the optic nerve is a classical model of neurodegeneration. It induces retinal ganglion cell death, a process also occurring in glaucoma and other optic neuropathies. We analyzed autophagy induction and cell survival following optic nerve transection (ONT) in mice. Our results demonstrate activation of autophagy shortly after axotomy with autophagosome formation, upregulation of the autophagy regulator Atg5 and apoptotic death of 50% of the retinal ganglion cells (RGCs) after 5 days. Genetic downregulation of autophagy using knockout mice for Atg4B (another regulator of autophagy) or with specific deletion of Atg5 in retinal ganglion cells, using the Atg5flox/flox mice reduces cell survival after ONT, whereas pharmacological induction of autophagy in vivo increases the number of surviving cells. In conclusion, our data support that autophagy has a cytoprotective role in RGCs after traumatic injury and may provide a new therapeutic strategy to ameliorate retinal diseases.

Descripción

La autofagia es un mecanismo de reciclaje por el cual la célula degrada proteínas y orgánulos enteros. Se ha descrito su implicación en desórdenes neurodegenerativos, desempeñando una función pro-supervivencia y en ocasiones pro-muerte, sin embargo su papel tras una lesión axonal resulta controvertido. La axotomía de nervio óptico constituye una lesión traumática del sistema nervioso central que conduce a la degeneración y muerte de las células ganglionares de la retina, hecho que también tiene lugar en otras alteraciones retinianas de alta prevalencia como el glaucoma. En el presente trabajo hemos demostrado que la autofagia juega un papel citoprotector para estas neuronas ya que su activación farmacológica rescata de la muerte, tanto in vitro como in vivo, mientras que su bloqueo genético exacerba la degeneración. Estos resultados nos llevan a pensar que la activación controlada de la autofagia podría representar una estrategia terapéutica en desórdenes retinianos menos agresivos que cursen con la pérdida de estas neuronas.

Imagen artículo Agosto

REFERENCIA DEL GRUPO E INVESTIGADOR
Natalia Rodríguez-Muela acaba de defender su tesis doctoral realizada en el Laboratorio de Autofagia en Desarrollo y Fisiopatología dirigido por Patricia Boya en el Centro de Investigaciones Biológicas del CSIC en Madrid. En nuestro laboratorio utilizamos modelos celulares y animales para comprender el papel de la autofagia en la fisiología y la patología de los organismos. Nuestro interés se centra en estudiar la autofagia durante el desarrollo y comprender su implicación en procesos esenciales como la proliferación, diferenciación y la muerte celular. Por otro lado queremos entender cómo defectos en autofagia pueden estar implicados situaciones patológicas como el cáncer y las enfermedades neurodegenerativas.

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