TIMP-2 and Ala + TIMP-2 inhibit VEGF-A–induced vascular permeability in vivo through PTP activity. (A) Quantification of in vivo permeability was performed using the modified Miles assay. Mice were injected intradermally with 50 μL of VEGF-A (1 μg/mL) with TIMP-2 (500nM) or Ala + TIMP-2. The results (mean ± SE) from 3 independent experiments are presented as nanograms of weight of extravasated Evans blue dye per milligram of weight of dermal tissue sample. **P < .01, compared with VEGF-A treatment alone. Representative Miles assay results are shown below the graph. (B) Mice were injected with VEGF-A with Ala + TIMP-2 or orthovanadate (5μM). The results (mean ± SE) from 4 independent experiments are presented as the fold increase of in vivo permeability in untreated controls. The amount of extravasated Evans blue dye in untreated controls was 18 ± 5.6 ng/mg tissue. *P < .05, compared with VEGF-A treatment alone. (C) Mice (5 mice in each group) were treated as in panel A, and tissue sections were analyzed by hematoxylin and eosin staining (original magnification ×400). Scale bars represent 50 μm. The black arrows indicate the extravasation of blood cells.