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Takeshi Iwase, Brian C. Oveson, Raquel Formica, Jikui Shen, Peter Adamson, Peter A. Campochiaro; Topical Pazopanib Blocks VEGF-Induced Vascular Leakage and Neovascularization in the Retina. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4880.
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Pazopanib is a potent multi-targeted tyrosine kinase inhibitor that blocks VEGF, PDGF, and c-kit (SCF) receptors. In this study, we sought to investigate the potential of topical pazopanib for treatment of diabetic macular edema (DME).
The effect of topically delivered pazopanib was tested on VEGF-induced vascular permeability by measuring the retina to lung leakage ratio (RLLR) and retina to renal leakage ratio (RRLR) of [3H]mannitol after intraocular injection of VEGF. The effect of topical pazopanib on VEGF-induced subretinal neovascularization (NV) was assessed in rhodopsin/VEGF (rho/VEGF) transgenic mice.
Intraocular injection of VEGF caused significant increases in the RLLR (p=0.023) and RRLR (p=0.032), and oral administration of 40 mg/kg/day of pazopanib by gavage significantly reduced the RLLR (0.93 to 0.56, p=0.004) and the RRLR (0.56 to 0.31, p=0.004) in VEGF-injected eyes. After intraocular injection of VEGF in both eyes, topical administration of 10 mg/ml pazopanib 3 times a day to one eye significantly reduced RLLR (0.89 vs. 0.56, p=0.048) and albumin immunofluorescence compared to the fellow eye. Treatment of one eye of rho/VEGF mice with 10 mg/ml of pazopanib 3 times a day significantly reduced the mean area of subretinal NV compared to that in fellow eyes (0.0057 vs. 0.0026 mm2, p=0.020).
A 10 mg/ml pazopanib given by topical eye drops was able to suppress VEGF-induced leakage and NV suggesting a potential utility of this formulation in patients with DME.
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