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C. Nakanishi, A. Jiang, H. Gao, X. Qiao; Inhibition of Subretinal Neovascularization With bFGF Neutralizing Antibody in VLDL Receptor Knockout Mice, an Animal Model of Retinal Angiomatous Proliferation. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2795.
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While VEGF is a dominant factor in pathological neovascularization in age-related macular degeneration (AMD), more evidence indicates that AMD has a complex etiology with different subtypes and involving multiple factors. This study examines the effect of blocking basic fibroblast growth factor (bFGF) on the development of subretinal neovascularization (SNV) in VLDL receptor knockout (vldlr-/-) mice, a model of retinal angiomatous proliferation (RAP).
At the onset of SNV at P14, vldlr-/- mice were treated by intravitreal injection in one eye with: 1 µl of anti-bFGF antibody, anti-VEGF antibody, or anti-CD105 (a key endothelial cell activation marker) antibody. The fellow eye was injected with the same volume of BSS solution as a control. After 7 or 14 days of survival, the animal eyes were harvested for isolectin staining. The total number of SNV was quantified in the whole mount retina using a fluorescent light microscope.
Anti-bFGF antibody treatment at the onset of SNV significantly reduced SNV in vldlr-/- mice at 14 days post-intravitreal injection. No significant SNV reduction was found at 7 days post-injection. Anti-VEGF antibody did not significantly reduce SNV at either time points. Antibody against CD105 also failed to reduce the number of SNV 7 days post-injection. Macrophage activation at 7 days post antibody injection was noticed by F4/80 staining.
Neutralizing antibody to bFGF significantly reduces SNV in vldlr-/- mice. These in vivo data support the conclusion that bFGF may be a potential therapeutic target for treating RAP. In addition, the differential responses to anti-angiogenic antibodies suggest different underlying mechanisms involving different subtypes of neovascular AMD.
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