JNK Inhibition Reduced Retinal Ganglion Cell Death after Ischemia/Reperfusion In Vivo and after Hypoxia In Vitro

• Published in: Advances in experimental medicine and biology Vol. 854; p. 677
• Main Authors: Produit-Zengaffinen, Nathalie, Favez, Tatiana, Pournaras, Constantin J, Schorderet, Daniel F
• Format: Journal Article
• Language: English
• Published: United States 01-01-2016
• Subjects: Animals; Apoptosis - drug effects; Apoptosis - physiology; Blotting, Western; Cell Hypoxia; Cell Line; Cell Survival - drug effects; Enzyme Activation - drug effects; Intraocular Pressure - physiology; JNK Mitogen-Activated Protein Kinases - antagonists & inhibitors; JNK Mitogen-Activated Protein Kinases - metabolism; Mice; Protein Kinase Inhibitors - pharmacology; Rats; Reperfusion Injury - metabolism; Reperfusion Injury - physiopathology; Retinal Ganglion Cells - drug effects; Retinal Ganglion Cells - metabolism; Retinal Ganglion Cells - physiology; In vivo; Therapy; Hypoxia; Ischemia; MAPK; JNK
• ISSN: 0065-2598
• DOI: 10.1007/978-3-319-17121-0_90

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.