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Abstract #46958 Published in IGR 13-3
Autophagy promotes survival of retinal ganglion cells after optic nerve axotomy in mice
Rodriguez-Muela N; Germain F; Marino G; Fitze PS; Boya PCell Death and Differentiation 2011;
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 Atg5(flox/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.Cell Death and Differentiation advance online publication, 24 June 2011; doi:10.1038/cdd.2011.88.
Department of Cellular and Molecular Medicine, 3D Lab, Development, Differentiation and Degeneration, Centro de Investigaciones Biologicas, CSIC, Ramiro de Maeztu 9, 28040 Madrid, Spain
Classification:
5.1 Rodent (Part of: 5 Experimental glaucoma; animal models)
11.8 Neuroprotection (Part of: 11 Medical treatment)
3.9 Pathophysiology (Part of: 3 Laboratory methods)
