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H.J. Koh, K. Bessho, L. Cheng, D. Bartsch, T.R. Jones, G. Bergeron-Lynn, W.R. Freeman; Treatment of Choroidal Neovascularization With an 8-Mer Peptide Derived From the Uroplasminogen Activator System . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3918.
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Purpose: CNV is the major cause of severe vision loss in AMD and is an important cause of vision loss in other diseases. Anti-angiogenesis therapies have focused on MMP inhibition and VEGF inhibition. We hypothesized that a peptide fragment derived from the uPA-uPAR system, which has been shown to be anti-angiogenic and anti-migratory would have a therapeutic effect in a rat model of laser induced CNV and that this inhibition would occur downstream from VEGF in the angiogenesis cascade. Methods:Forty Brown Norway rats received 8 spots of diode laser treatment in one eye applied in a circle around the optic nerve of sufficient intensity to cause a bubble and rupture of Bruch’s membrane. Ten rats were treated with subcutaneous peptide (200mg/kg/day) and 10 with PBS injections. Two weeks and 7 weeks after induction of CNV, the eyes were studied with confocal FA and ICG angiography; CNV was also confirmed histopathologically. An additional 20 eyes were treated as part of a high dose regimen; In these eyes, the peptide was administered at a dose of 400 mg/kg/day, whereas double amount of PBS injected in their control. Results: At the 200 mg/kg/day dose, the incidence of CNV, defined angiographically, was 31.4 % in the treatment group vs. 50.6 % in the control group. This corresponded to a 37.9% reduction in induced CNV (P= 0.03). At the 400 mg/kg/day dose, the incidence of CNV was 13.4% in the treatment group vs. 44.7% in the control group. This corresponded to a 70.0% reduction in induced CNV (P=0.0124). There was no evidence of adverse effects of the compound. Conclusion:The 8-mer uPA fragment given subcutaneously (or potentially by other routes) may be a good candidate for the treatment of CNV in patients with AMD. Further studies to characterize the ocular pharmacokinetics and effect on normal tissues and to determine the maximal dose needed for treatment should be performed.
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