Retinal vascular permeability suppression by topical application of a novel VEGFR2/Src kinase inhibitor in mice and rabbits
J. Clin. Invest. Lea Scheppke, et al. 118:2337 doi:10.1172/JCI33361 [
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Figure 1PP1 inhibits VEGF-induced retinal vascular permeability. (
A–
C) Fluorescein dextran–perfused retinal whole mounts from mice that received systemic vehicle and either intravitreal PBS (
A) or VEGF (
B) versus systemic PP1 and intravitreal VEGF (
C). Shown is the absence of leakage in eyes given both VEGF and PP1 (
C, higher magnification) compared with VEGF-treated eyes in the absence of an Src kinase inhibitor, which have areas of both focal and diffuse dextran extravasation (
B). (
D) Vascular permeability as measured by retinal EB dye accumulation, with and without drug treatments. Error bars indicate SEM.
n = eyes per group. EB leakage: intravitreal PBS and systemic vehicle, 2.81 ± 0.51 (SEM). VEGF/vehicle, 8.69 ± 1.43; PBS/SKI-606, 1.62 ± 0.37; VEGF/SKI-606, 1.98 ± 0.43; PBS/PP1, 1.38 ± 0.27; VEGF/PP1, 1.85+0.46 Retinal vascular permeability factor is a measure of [concentration of EB dye in the retina]/[concentration of EB dye in the plasma × circulation time]. **
P < 0.01. Original magnification, ×4 (
A,
B); ×10 (
C).