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 2
Temporal changes of lymphatic function visualized by lymphoscintigraphy. (a and b) Orientation of the lymphoscintigraphic images. In normal ears, lymphatic flow assumes a linear pattern and the draining LNs are clearly visible. In the operated ear, the lymphatic passages were blocked, resulting in backward diffusion and no visualization of LNs. (c and d) Temporal changes in the saline group. Even at 12 weeks (d), lymphoscintigraphy demonstrates substantial impairment of lymphatic drainage of the saline-injected ear, indicated by dermal backflow and faint visualization of the LNs. (e and f) Temporal changes in the VEGF-C group. In the phVEGF-C–transfected ears, there was remarkable improvement of draining function. At 12 weeks, a linear passage of radiotracer, decreased dermal backflow, and increased uptake by LNs were observed. (g and h) Representative lymphoscintigraphic images and calculation of radioactivity index from the saline (g) and VEGF-C group (h). To quantitatively compare lymphatic drainage, the radioactivity within the ear was counted. Net radioactivity of the ear was obtained by subtracting γ counts at injection sites (arrows) from the total counts of the ear. The radioactivity index is the ratio of radioactivity of the operated ear divided by the radioactivity of the normal ear; this was used to compare lymphatic drainage function of the lymphedema ears. Higher ratios indicate more persistent radioactivity and less lymphatic drainage. (i) Comparison between the saline and VEGF-C groups shows the values were consistently lower in the VEGF-C group at 4, 8, and 12 weeks. *P < 0.05; **P < 0.01.