Subconjunctival Injection of XG-102, a c-Jun N-Terminal Kinase Inhibitor Peptide, in the Treatment of Endotoxin-Induced Uveitis in Rats.

Détails

Ressource 1Télécharger: BIB_85B3BE11E80B.P001.pdf (785.01 [Ko])
Etat: Public
Version: Author's accepted manuscript
ID Serval
serval:BIB_85B3BE11E80B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Subconjunctival Injection of XG-102, a c-Jun N-Terminal Kinase Inhibitor Peptide, in the Treatment of Endotoxin-Induced Uveitis in Rats.
Périodique
Journal of Ocular Pharmacology and Therapeutics
Auteur(s)
El Zaoui I., Touchard E., Berdugo M., Abadie C., Kowalczuk L., Deloche C., Zhao M., Naud M.C., Combette J.M., Behar-Cohen F.
ISSN
1557-7732 (Electronic)
ISSN-L
1080-7683
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
31
Numéro
1
Pages
17-24
Langue
anglais
Notes
Publication types: Journal Article Publication Status: ppublish
Résumé
Abstract Purpose: XG-102, a TAT-coupled dextrogyre peptide inhibiting the c-Jun N-terminal kinase, was shown efficient in the treatment of experimental uveitis. Preclinical studies are now performed to determine optimal XG-102 dose and route of administration in endotoxin-induced uveitis (EIU) in rats with the purpose of clinical study design.
METHODS: EIU was induced in Lewis rats by lipopolysaccharides (LPS) injection. XG-102 was administered at the time of LPS challenge by intravenous (IV; 3.2, 35 or 355 μg/injection), intravitreal (IVT; 0.08, 0.2 or 2.2 μg/eye), or subconjunctival (SCJ; 0.2, 1.8 or 22 μg/eye) routes. Controls received either the vehicle (saline) or dexamethasone phosphate injections. Efficacy was assessed by clinical scoring, infiltrating cells count, and expression of inflammatory mediators [inducible nitric oxide synthase (iNOS), cytokine-induced neutrophil chemoattractant-1 (CINC-1)]. The effect of XG-102 on phosphorylation of c-Jun was evaluated by Western blot.
RESULTS: XG-102 demonstrated a dose-dependent anti-inflammatory effect in EIU after IV and SCJ administrations. Respective doses of 35 and 1.8 μg were efficient as compared with the vehicle-injected controls, but only the highest doses, respectively 355 and 22 μg, were as efficient as dexamethasone phosphate. After IVT injections, the anti-inflammatory effect of XG-102 was clinically evaluated similar to the corticoid's effect with all the tested doses. Regardless of the administration route, the lowest efficient doses of XG-102 significantly decreased the ration of phospho c-Jun/total c-Jun, reduced cells infiltration in the treated eyes, and significantly downregulated iNOS and CINC-1 expression in the retina.
CONCLUSION: These results confirm that XG-102 peptide has potential for treating intraocular inflammation. SCJ injection appears as a good compromise to provide a therapeutic effect while limiting side effects.
Pubmed
Web of science
Open Access
Oui
Création de la notice
02/02/2015 15:32
Dernière modification de la notice
20/08/2019 15:45
Données d'usage