VEGF-C gene therapy augments postnatal lymphangiogenesis and ameliorates secondary lymphedema
J. Clin. Invest. Young-sup Yoon, et al. 111:717 doi:10.1172/JCI15830 [Go to this article.]

Figure 1
(a–d) Rabbit ear model of lymphedema: effect of phVEGF-C gene therapy. (a) Postoperative appearance of the dorsal surface of the rabbit ear. Lymphedema surgery leaves a gap of cartilage crossed only by the skin bridge. (b) A view under a surgical microscope after lifting up the skin bridge showing neurovascular bundle. Lymphatic vessels were visualized as blue lines (arrows) due to the uptake of Evans blue. Ear thickness (c) and volume (d) show consistent differences between the VEGF-C and saline groups over 12 weeks. *P < 0.05; **P < 0.01. (e–i) Decreased skin thickness after phVEGF-C transfer in a rabbit lymphedema model. Photos show cross sections of the skin after elastic-tissue trichrome staining 8 weeks after lymphedema surgery. Compared with normal ears (e and g), operated ears (f and h) had fibrofatty tissue deposition and thus greater skin thickness. The phVEGF-C–transfected ear shown in h shows less fibrosis and decreased thickness compared with the saline-injected ear (f), which demonstrates other characteristic features of lymphedema, such as profound epidermal hyperplasia and papillomatosis. (i) Measurement of skin thickness from histologic sections shows a significant difference between the saline and VEGF-C groups (P < 0.05). *P < 0.05; **P < 0.01. Scale bar, 500 μm. Normal-S and Normal-V indicate unoperated ears from the saline and VEGF-C groups, respectively; LE indicates lymphedema-operated ears.