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Ikram El-Zaoui, Elodie Touchard, Marianne Berdugo Polak, Claire Abadie, Catherine Deloche, Jean-Marc Combette, Francine Behar-Cohen; Evaluation of XG-102 effects in the treatment of endotoxin-induced uveitis in rats. Invest. Ophthalmol. Vis. Sci. 2013;54(15):113.
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To confirm the efficacy of XG-102 (JNK Inhibitor) in the treatment of endotoxin-induced uveitis (EIU) in rats, XG-102 dose-effect was evaluated using different routes of administration.
EIU was induced in Lewis rats by LPS injection. XG-102 was administered at the time of LPS challenge either by intravenous (IV, 3.2, 35 or 355 µg/injection), intravitreal (IVT, 0.08, 0.2 or 2.2 µg/eye) or sub-conjunctival (SCJ, 0.2, 1.8 or 2.2 µg/eye) injections. Controls received either the vehicle or Dexamethasone phosphate injections. Clinical effects were scored at the peak of the disease(24 hours after LPS). XG-102 targeting was controlled by Western-blotting the phosphorylated c-Jun in the “RPE-Choroid” complex. The anti-inflammatory effects were evaluated using quantification of cells infiltration in ocular tissues and evaluation of the expression of inflammatory mediators(iNOS at the mRNA levels in the neuroretina.
XG-102 clinically demonstrated adose-dependent anti-inflammatory effect in EIU after IV and SCJ administrations. The respective doses of 35 µg and 1.8 µg were efficient as compared with the vehicle-injected controls, and the highest doses, respectively 355 µg and 22 µg, were as efficient as Dexamethasone. After IVT injections, the anti-inflammatory effect of XG-102 was clinically evaluated similar to the corticoid’s effect with all the tested doses. Whatever the route administration tested, the lowest efficient doses of XG-102 targeted efficiently the c-Jun N-terminal kinase; reduce cells infiltration in the treated eyes and iNOS expression in the retina.
These results confirm that XG-102 has potential for treating intraocular inflammation. The subconjunctival route will be further investigated in humans.
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