Increased wrinkle formation in VEGF-overexpressing mice after long-term UVB irradiation with 3.6 × 10^-2 J/cm². (A) Dorsal skin of nonirradiated wild-type and VEGF transgenic mice. After 10 weeks of UVB irradiation (total dose, 7.92 × 10^-1 J/cm²), wild-type mice did not show any macroscopic skin alterations (B, left side), whereas VEGF transgenic mice developed photodamage with wrinkle formation and slight erythema (B, right side) (representative images; n = 10 per genotype). Skin replicas of wild-type and VEGF-overexpressing mice showed no signs of wrinkle formation or texture damage (C-D), nor did those of wild-type mice treated with UVB (E). VEGF-overexpressing mice treated with long-term UVB irradiation, however, did show wrinkle formation and texture damage (F). Histologic analysis and hematoxylin-eosin staining (G-J) revealed that the skin of nonirradiated mice of both genotypes (G-H) and of UVB-irradiated wild-type mice (I) did not reveal any major histologic abnormalities. The skin of UVB-irradiated VEGF-overexpressing mice, however, showed signs of epidermal hyperplasia, edema, inflammatory cell infiltration, and increased vascularization in the papillary dermis (J). LUNA staining (K-N) revealed an irregular organization of elastic and collagen fibers in the papillary dermis of UVB-treated VEGF transgenic mice (N, arrowheads) compared with nonirradiated VEGF transgenic mice (L, arrows) or with wild-type littermates with or without UVB irradiation (K, M). Scale bars, 50 μm. For panels C-F, a Leica M2FLIII microscope equipped with a 1.25 objective (Leica Microsystems, Allendale, NJ) was used. A Niko E-600 microscope equipped with a Plan Fluor 40 × objective with an aperture of 0.75 was used for panels G-N.