Purchase this article with an account.
Sadullah Keles, Zekai Halici, Hasan Tarik Atmaca, Muhammed Yayla, Kenan Yildirim, Metin Ekinci, Erol Akpinar, Durdu Altuner, Ozgur Cakici, Zafer Bayraktutan; The Ocular Endothelin System: A Novel Target for the Treatment of Endotoxin-Induced Uveitis With Bosentan. Invest. Ophthalmol. Vis. Sci. 2014;55(6):3517-3524. doi: 10.1167/iovs.14-14193.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
We compared the anti-inflammatory effects of bosentan and dexamethasone in endotoxin-induced uveitis (EIU).
Endotoxin-induced uveitis was induced by subcutaneous injection of lipopolysaccharide (LPS, 200 μg) in Wistar rats. Rats were divided randomly into 10 groups (n = 6). Bosentan at doses of 50 and 100 mg/kg were administered orally 1 hour before and 12 hours after LPS injection, and dexamethasone was administered by intraperitoneally 30 minutes before and 30 minutes after LPS injection at a dose of 1 mg/kg. Data were collected at two time points for each control and treatment; animals were killed at either 3 or 24 hours after LPS injection. Histopathologic evaluation and aqueous humour measurements of TNF-α level were performed, and endothelin-1 (ET-1), inducible nitric oxide synthase (iNOS), and endothelin receptor A and B (EDNRA and B) expression were analyzed.
The group treated with 100 mg/kg bosentan at 24 hours displayed significantly milder uveitis and fewer inflammatory cells compared to LPS-injected animals, and there were similar findings in the dexamethasone-treated group at 24 hours. The TNF-α levels in the dexamethasone treatment group were lower than those in the LPS-induced uveitis control group (P < 0.05); however, there was no difference between the dexamethasone and bosentan treatment groups at 3 and 24 hours after LPS administration. Bosentan treatment at doses of 50 and 100 mg/kg significantly decreased iNOS expression compared to LPS-injected animals (P < 0.001). The ET-1 expression was suppressed significantly by bosentan and dexamethasone at 3 and 24 hours after LPS administration (P < 0.001). The EDNRA expression in the bosentan treatment groups was statistically significantly lower than that in the LPS-induced uveitis control group at 3 and 24 hours after LPS administration (P < 0.05).
Bosentan reduces intraocular inflammation and has similar effects as dexamethasone in a rat model of EIU.
This PDF is available to Subscribers Only