Autophagy promotes survival of retinal ganglion cells after optic nerve axotomy in mice.

Détails

ID Serval
serval:BIB_312819C400CC
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Autophagy promotes survival of retinal ganglion cells after optic nerve axotomy in mice.
Périodique
Cell Death and Differentiation
Auteur(s)
Rodríguez-Muela N., Germain F., Mariño G., Fitze P.S., Boya P.
ISSN
1476-5403 (Electronic)
ISSN-L
1350-9047
Statut éditorial
Publié
Date de publication
2012
Peer-reviewed
Oui
Volume
19
Numéro
1
Pages
162-169
Langue
anglais
Résumé
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.
Mots-clé
Animals, Apoptosis/physiology, Autophagy/physiology, Axotomy, Cell Culture Techniques, Cell Survival, Cysteine Endopeptidases/genetics, Cysteine Endopeptidases/metabolism, Disease Models, Animal, Gene Expression Regulation, Mice, Mice, Knockout, Microtubule-Associated Proteins/genetics, Microtubule-Associated Proteins/metabolism, Optic Nerve/physiology, Optic Nerve Injuries/physiopathology, Retinal Ganglion Cells/physiology
Pubmed
Web of science
Open Access
Oui
Création de la notice
29/05/2011 21:30
Dernière modification de la notice
20/08/2019 13:16
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