PURPOSE. This study evaluates the effects of the gold nanoparticle in endotoxin-induced uveitis in rats.METHODS. Adult male Wistar rats were divided into five groups: saline þ saline, lipopolysaccharide (LPS) þ saline, LPS þ prednisolone, LPS þ gold salt (GS) and LPS þ gold nanoparticle (GNP). Two hours after LPS administration, prednisolone acetate 1%, GS, and GNP were topically applied to both eyes of rats and repeated every 6 hours for 24 hours. After 24 hours, rats were anesthetized and aqueous humor was sampled and the irides were removed. Aqueous humor TNF-a, myeloperoxidase activity were determined. Irides oxidative damage and content of toll-like receptor 4 (TLR4) and nuclear factor-jB (NF-jB) were determined.RESULTS. The administration of LPS-induced eye inflammatory response characterized by an increase in aqueous humor TNF-a, myeloperoxidase, and by irides oxidative damage. All these parameters were decreased by the administration of GNP. Since the inflammatory response secondary to LPS administration depends, in part, to the activation of the TLR4-NF-jB pathway we demonstrated here that a potential mechanism to explain the GNP effects was the decrease on TLR4 content and NF-jB activation.CONCLUSIONS. These findings suggest that topical GNP decreases intraocular inflammation and oxidative damage by interfering in the TLR4-NF-jB pathway. Oxidative stress is also suggested to be pathogenic by inducing inflammation in the eye. 10,11Endotoxin-induced uveitis (EIU) is an established animal model for ocular inflammation. These animals develop acute bilateral anterior inflammation, characterized by a breakdown of the blood-ocular barrier and accumulation of inflammatory cells. 12 Oxidative biomarkers are shown to be elevated in EIU, suggesting that inflammation and oxidative stress cooperatively contribute to its pathogenesis. 13Over the past few decades, gold nanoparticles (GNP) have become the object of special interest due to their antiinflammatory activity.14 Gold compounds have been used as anti-inflammatory treatment against rheumatoid arthritis for more than 50 years. [15][16][17] The molecular mechanisms of gold actions include modulation of pro-inflammatory, as well as inactivation of phagolysosomal enzymes and inhibition of NF-jB. 18,19 In view of these anti-inflammatory properties of gold compounds, the present study investigates the potential applications of GNP in the modulation of the inflammatory response in an animal model of uveitis. MATERIALS AND METHODS GNPs PreparationGNP were prepared as described by Turkevich et al. 20 In brief, glass vials were washed in aqua regia and rinsed in ultrapure water, then aurochloric acid solution (0.2 mM) was gently warmed up to 908C and sodium citrate (39 mM) was added. After 20 minutes of vigorous stirring and refluxing, the solution was cooled at room temperature (20 6 28C) and the GNP were purified by serial centrifugations at 9000g for 10 minutes, followed by supernatant removing and ultra pure water rinsing. The resulting powder was resuspended in s...

These findings suggest that GRP participates in the inflammatory response in an animal model of uveitis, making GRPR a target for new therapeutic options in the treatment of uveitis.