Figure 4.
Systemic treatment of wild-type mice with a neutralizing anti-VEGF antibody results in reduced photosensitivity but does not inhibit tissue repair. The dorsal skin of IgG-treated wild-type control mice appeared healthy after a single irradiation with 3.6 × 10-2 J/cm2 (A), but edema was observed after exposure to 5.4 × 10-2 J/cm2 UVB (C). Systemic blockade of VEGF inhibited tissue swelling after a single UVB irradiation with 5.4 × 10-2 J/cm2 (D). After UVB exposure of 7.2 × 10-2 J/cm2, tissue edema and inflammatory cell infiltration were pronounced in control IgG (E) and anti–VEGF antibody-treated mice (F). Hematoxylin-eosin stain (A-F). Degradation of extracellular matrix was found in control IgG-treated mice after UVB exposure of 7.2 × 10-2 J/cm2 (G), but not in anti–VEGF antibody-treated mice (H). Trichrome stain (G-H). Immunofluorescence analysis with an antibody against CD31 revealed dilated vessels in the papillary dermis of control IgG-treated mice by 48 hours after UVB irradiation with 5.4 × 10-2 J/cm2 (I), but not in anti–VEGF antibody-treated mice (J). Nuclei are labeled blue (Hoechst stain). At 14 days after exposure to a UVB dose of 7.2 × 10-2 J/cm2, no signs of tissue edema or cutaneous damage (K-L, hematoxylin-eosin stains) or extracellular matrix alterations (M-N, trichrome stains) were found in control IgG-treated and in anti–VEGF antibody-treated mice. Scale bars, 200 μm (A-F, K-L); 100 μm (G-J, M-N). A Plan Fluor 10 × objective with an aperture of 0.30 was used for panels A-F, K, and L. A Plan Fluor 20 × objective with an aperture of 0.50 was used for panels G-J, M, and N. Computer-assisted morphometric analysis revealed reduced vessel area (O) and reduced vessel size (P) in anti–VEGF antibody-treated mice (▪) compared with control IgG-treated mice (□) 48 hours after UVB exposure. Vessel density (number of vessels per square millimeter) was not significantly different between each group (Q). Data are expressed as mean ± SD (n = 5). **P < .01; *P < .05.