Titre
Role of the c-Jun N-terminal kinase pathway in retinal excitotoxicity, and neuroprotection by its inhibition.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Bessero, A.C.
Auteure/Auteur
Chiodini, F.
Auteure/Auteur
Rungger-Brändle, E.
Auteure/Auteur
Bonny, C.
Auteure/Auteur
Clarke, P.G.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1471-4159
Statut éditorial
Publié
Date de publication
2010-06
Volume
113
Numéro
5
Première page
1307
Dernière page/numéro d’article
1318
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
Retinal excitotoxicity is associated with retinal ischemia, and with glaucomatous and traumatic optic neuropathy. The present study investigates the role of c-Jun N-terminal kinase (JNK) activation in NMDA-mediated retinal excitotoxicity and determines whether neuroprotection can be obtained with the JNK pathway inhibitor, D-form of JNK-inhibitor 1 (D-JNKI-1). Young adult rats received intravitreal injections of 20 nmol NMDA, which caused extensive neuronal death in the inner nuclear and ganglion cell layers. This excitotoxicity was associated with strong activation of calpain, as revealed by fodrin cleavage, and of JNK. The cell-permeable peptide D-JNKI-1 was used to inhibit JNK. Within 40 min of its intravitreal injection, FITC-labeled D-JNKI-1 spread through the retinal ganglion cell layer into the inner nuclear layer and interfered with the NMDA-induced phosphorylation of JNK. Injections of unlabeled D-JNKI-1 gave unprecedentedly strong neuroprotection against cell death in both layers, lasting for at least 10 days. The NMDA-induced calpain-specific fodrin cleavage was likewise strongly inhibited by D-JNKI-1. Moreover the electroretinogram was partially preserved by D-JNKI-1. Thus, the JNK pathway is involved in NMDA-mediated retinal excitotoxicity and JNK inhibition by D-JNKI-1 provides strong neuroprotection as shown morphologically, biochemically and physiologically.
Sujets
PID Serval
serval:BIB_AE90EA937D2B
PMID
Open Access
Oui
Date de création
2010-05-28T08:18:29.653Z
Date de création dans IRIS
2025-05-20T23:21:53Z