Purchase this article with an account.
J. Onderka, F. Bock, T. Dietrich, B. Pytowski, F. Kruse, C. Cursiefen; Inflammatory Corneal Lymphangiogenesis is Inhibited by Blocking Vegfr3–Signalling . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3909.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Inflammatory corneal hem– and lymphangiogenesis occurring both prior to as well as after penetrating keratoplasty significantly increases the risk for subsequent immune rejections. Purpose of this study was to analyze whether the blocking anti–VEGFR3 antibody mF4–31C1 is able to inhibit the outgrowth of pathologic new lymphatic vessels in a mouse model of suture–induced, inflammatory corneal neovascularization. The potency of this antibody has been recently demonstrated in a mouse model of spontaneous, non–inflammatory corneal hem– and lymphangiogenesis.
Three interrupted 11–0 nylon sutures were placed into the corneal stroma of BALB/c mice (6 weeks old) and left in place for seven days to induce neovascularization. The treatment group (n=9) received the anti–VEGFR3 antibody F4–31C1 intraperitoneally at day of surgery and three days later (0.5 mg/mouse). Control mice received an equal amount of control IgG solution (Jackson Immunoresearch, Inc. CA). For immunohistochemistry, corneal flat mounts were stained with LYVE–1 as a specific lymphatic vascular endothelial marker and CD31 as panendothelial marker. Morphometry was performed with the image analysis software analySIS^B (Soft Imaging Systems GmbH, Münster, Germany).
To improve the objectivity and precision of the morphometrical analysis, we established a modified analysing method using grey filter sampling on monochromatic pictures. The F4–31C1 antibody treated mice displayed nearly complete inhibition of lymphangiogenesis compared with IgG controls (p < 0.006).
Inflammatory corneal lymphangiogenesis seems to depend on VEGFR3–signalling. By blocking this lymphangiogenic receptor the ingrowths of lymph vessels can be inhibited almost completely. This specific anti–VEGFR3 antibody could be used to inhibit lymphangiogenesis after keratoplasty to reduce neovascularization and thereby promote graft survival.
This PDF is available to Subscribers Only