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Felix Bock, Ann-Charlott Schneider, Megan Baldwin, Claus Cursiefen; Specific Inhibition of Inflammatory Corneal Lymphangiogenesis by Topical Inhibition of VEGF-C and -D. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3537.
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© 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. The purpose of this study was to analyze whether a VEGF-C/D trap (OPT-302; Circadian Technologies Ltd/Opthea Pty Ltd, Australia) is able to inhibit the outgrowth of pathologic new lymphatic vessels in a mouse model of suture-induced, inflammatory corneal neovascularization by application as eye drops
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 VEGF-C/D trap as eye drops three times per day (100µg/drop). Control mice received an equal amount of control IgG solution. 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 Cell^F (Olympus, Germany).
The VEGF-C/D trap treated mice displayed nearly complete inhibition of lymphangiogenesis compared with IgG controls (p < 0.01). Furthermore, significantly more macrophages were present in the VEGF-C/D trap treated group (p < 0.001).
Corneal VEGF-C and D induce inflammatory lymphangiogenesis. By blocking these lymphangiogenic growth factors locally the ingrowths of lymph vessels can be inhibited almost completely. The absence of lymphatic vessels may lead to an accumulation of macrophages either trapped due to lacking lymphatic drainage or hampered to integrate into budding lymphatic vessels. This specific VEGF-C/D trap could be used to inhibit lymphangiogenesis after (corneal) transplantation to promote graft survival.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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