title: JNK Inhibition Reduced Retinal Ganglion Cell Death after Ischemia/Reperfusion In Vivo and after Hypoxia In Vitro.
abstract: Mitogen-activated protein kinases (MAPKs) are key regulators that have been linked to cell survival and death. Among the main classes of MAPKs, c-jun N-terminal kinase (JNK) has been shown to mediate cell stress responses associated with apoptosis. In Vitro, hypoxia induced a significant increase in 661W cell death that paralleled increased activity of JNK and c-jun. 661W cells cultured in presence of the inhibitor of JNK (D-JNKi) were less sensitive to hypoxia-induced cell death. In vivo, elevation in intraocular pressure (IOP) in the rat promoted cell death that correlated with modulation of JNK activation. In vivo inhibition of JNK activation with D-JNKi resulted in a significant and sustained decrease in apoptosis in the ganglion cell layer, the inner nuclear layer and the photoreceptor layer. These results highlight the protective effect of D-JNKi in ischemia/reperfusion induced cell death of the retina.
authors.affiliation: Faculty of Life Sciences, Swiss Federal Institute of Technology, Lausanne, Switzerland. nathalie.produit-zengaffinen@irovision.ch.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Produit-Zengaffinen
authors.affiliation: Faculty of Life Sciences, Swiss Federal Institute of Technology, Lausanne, Switzerland. tatiana.favez@irovision.ch.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Favez
authors.affiliation: Department of Ophthalmology, Geneva University Hospitals, Geneva, Switzerland. constantin.pournaras@lacolline.ch.
authors.forename: Constantin J
authors.initials: CJ
authors.lastname: Pournaras
authors.affiliation: Faculty of Life Sciences, Swiss Federal Institute of Technology, Lausanne, Switzerland. daniel.schorderet@irovision.ch.|IRO-Institute for Research in Ophthalmology, Av du Grand-Champsec 64, Sion, Switzerland. daniel.schorderet@irovision.ch.|Department of Ophthalmology, University of Lausanne, Lausanne, Switzerland. daniel.schorderet@irovision.ch.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Schorderet
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western; D015687:Cell Hypoxia; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D007429:Intraocular Pressure / Q000502:physiology; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
chemical_list: D047428:Protein Kinase Inhibitors; D048031:JNK Mitogen-Activated Protein Kinases
keywords: Hypoxia; In vivo; Ischemia; JNK; MAPK; Therapy