title: Autophagy promotes survival of retinal ganglion cells after optic nerve axotomy in mice.
abstract: 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.
authors.affiliation: Department of Cellular and Molecular Medicine, Centro de Investigaciones Biológicas, CSIC, Madrid, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Rodríguez-Muela
authors.forename: F
authors.initials: F
authors.lastname: Germain
authors.forename: G
authors.initials: G
authors.lastname: Mariño
authors.forename: P S
authors.initials: PS
authors.lastname: Fitze
authors.forename: P
authors.initials: P
authors.lastname: Boya
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001343:Autophagy / Q000502:physiology*; D000071187:Autophagy-Related Protein 5; D000071183:Autophagy-Related Proteins; D019771:Axotomy; D018929:Cell Culture Techniques; D002470:Cell Survival; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009900:Optic Nerve / Q000502:physiology*; D020221:Optic Nerve Injuries / Q000503:physiopathology*; D012165:Retinal Ganglion Cells / Q000502:physiology*
chemical_list: C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; D000071183:Autophagy-Related Proteins; D008869:Microtubule-Associated Proteins; C582881:Atg4b protein, mouse; D003546:Cysteine Endopeptidases