Cabozantinib, a Multityrosine Kinase Inhibitor of MET and VEGF Receptors Which Suppresses Mouse Laser-Induced Choroidal Neovascularization

Figure 5

CBZ oral gavage mitigates CNV leakage and the CNV lesion area and restrains the phosphorylation of MET and VEGFR2. (a) Schematic diagram of the experimental procedure. The mice were left untreated (300 mg/kg/day CBZ, negative control) or were treated (control group) with a laser at day 0. Additionally, 200 or 300 mg/kg/day of CBZ was added to mouse daily fodder until day 14 when the mouse eye tissues were collected and analyzed. ICGA (b) (a, b, c, and c) and FFA (b) (e, f, g, and h) were performed, and (c) fluorescein leakage in CNV lesions was graded at 14 d after CNV in the control (n = 32 lesions), 200 mg/kg/day CBZ (n = 30 lesions), and 300 mg/kg/day CBZ (n = 32 lesions) groups. (b, d) (i-1, j-1, k-1, l-1, i-2, j-2, k-2, l-2, i-3, j-3, k-3, l-3) The mouse CNV lesion area 7 d after CNV induction was assessed by the staining of choroidal flat-mounts with fluorescent IB4 and phalloidin. Scale bar = 100 μm. n = 8/group. vs. the control group. (e) The protein levels of HGF, p-MET, MET, VEGF, p-VEGFR2, and p-VEGFR2 in the negative control, control, 200 mg/kg/day CBZ, and 300 mg/kg/day CBZ groups were detected by Western blotting. (f) Quantification of the HGF, p-MET, VEGF, and p-VEGFR2 protein levels in each group. n = 6/group. vs. the negative control group; and vs. the control group; NS, not significant.

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