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A. Das, P.G. McGuire, T.R. Jones, N. Talarico, E. Warren; The uPA/uPAR System in Choroidal Neovascularization: A Target for Anti-Angiogenic Therapy . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3941.
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Purpose: We have previoulsy shown a role for urokinase (uPA) and its receptor uPAR during retinal neovasculariztaion in an animal model. The purpose of this study was to examine whether inhibition of this proteolytic system can suppress the extent of choroidal neovascularization (CNV). Methods: CNV was induced in C57/Bl6 mice by laser photocoagulation (Argon green, 100 micron spot size, 0.1 sec duration and 120mW intensity) using the slit lamp delivery system. Production of a vaporization bubble indicating rupture of Bruch's membrane, was used as an endpoint during laser treatment. Over the next two weeks following laser treatment, animals were treated with an IP injection of an inhibitor of uPA /uPAR interaction (A6 peptide, 100mg/kg). Control, laser treated, animals received IP injections of PBS for the same period of time. Following treatment, eyes were removed and examined by staining frozen sections with GSA lectin. The extent of neovascularization in the burn areas was quantitated using the MetaMorph image analysis software. Results: Histological analysis of mice treated with A6 showed significant inhibition of CNV (up to 70%, p<0.05) with no detectable toxic side effects. Conclusions: Significant inhibition of CNV was seen when cell-surface associated uPA/uPAR activity was prevented with the peptide A6. These data suggest a potential new anti-angiogenic therapy for CNV as seen in age-related macular degeneration.
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