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D. Skondra, K. Noda, H. Yu, A. Schering, E. Gragoudas, A. Hafezi-Moghadam; Aprotinin Reduces Intraocular Inflammation in Endotoxin Induced Uveitis. Invest. Ophthalmol. Vis. Sci. 2009;50(13):6046.
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Aprotinin is a broad-spectrum serine protease inhibitor. Recently we showed that aprotinin reduces retinal vascular permeability in VEGF-induced and early diabetic blood retinal barrier breakdown. Aprotinin also decreases retinal thickness and leptin expression in experimental uveitis, however, its effect on ocular inflammation remains unknown. Here, we investigate the potency of aprotinin for suppressing intraocular inflammation in endotoxin induced uveitis (EIU).
EIU was induced by hind footpad injections of LPS (200µg) in male Lewis rats. Animals were treated with 50,000 KIU Aprotinin (5ml of Trasylol) or the equivalent volume of saline, intraperitoneally q8 hrs for 24 hrs. Intraocular inflammation was evaluated 24 hrs after LPS injection. The number of infiltrated cells and protein concentration in the aqueous humor of the anterior chamber (AC) was quantified in normal and EIU animals with or without aprotinin treatment. Retinal leukocyte adhesion was quantified using the Concanavalin A assay. Retinal vascular permeability was measured with the Evans Blue (EB) technique.
Aprotinin treatment of EIU animals significantly reduced the AC cell accumulation by 85% (n=14, p<0.01) and protein concentration by 77% (n=13, p<0.01), compared with vehicle-treated controls (n=12 and n=10 respectively), 24h after disease induction. Aprotinin significantly reduced retinal vascular leakage by 73% (n=14, n=10, p=0.01) and retinal leukocyte adhesion by 80% (n=8 and n=7 respectively, p<0.05).
These data suggest that aprotinin is an effective inhibitor of ocular inflammation in experimental uveitis. Though, the underlying mechanisms are not well understood, use of protease inhibitors may become a novel therapeutic approach in treatment of acute ocular inflammation.
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