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Felix Bock, Ann-Charlott Schneider, Alexander Aslanidis, Marcus Karlstetter, Harald Neumann, Thomas Langmann, Claus Cursiefen; PolySia avDP20 modulates macrophage-associated corneal hem- and lymphangiogenesis. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3318. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Macrophages are intimately involved in corneal hem- and lymphangiogenesis. Furthermore, macrophages are immune modulated by polysialic acids of the glycocalyx. Here we tested if eye drops of low molecular weight polysialic acid with average degree of polymerization 20 (polySia avDP20) modulates inflammatory corneal hem- and lymphangiogenesis.
Three interrupted 11-0 nylon sutures were placed into the corneal stroma of C57BL/6 mice (6 weeks old) and left in place for 14 days to induce neovascularization. The treatment group (n=10) received polySia avDP20 as eye drops four times per day (1µg/µl; 3µl/drop). Control mice received an equal amount of PBS. For immunohistochemistry, corneal flat mounts were stained with LYVE-1 as a specific lymphatic vascular endothelial marker and CD31 as pan endothelial marker. Morphometry was performed with the image analysis software Cell^F (Olympus, Germany). Additionally, macrophages in the cornea as well as immune cells from the draining lymph nodes were analysed.
PolySia avDP20 eye drops significantly inhibits the outgrowth of corneal blood vessels (control: 31.13% vs polySia avDP20: 20.36%). Furthermore, also corneal lymphangiogenesis was down regulated (control: 5.7% vs polySia avDP20: 3.3%). In contrast, the number of macrophages was significantly increased in the cornea (cells per cornea: control: 3246 ± 399,9 vs polySia avDP20: 6060 ± 708,9). Interestingly, in the draining lymph nodes CD11c positive dendritic cells showed significantly less MHC class II expression in the PolySia avDP20 group.
PolySia avDP20 effectively modulates the corneal immune response against an inflammatory stimulus. These results indicate the use of PolySia avDP20 as a new, topical applicable, anti-inflammatory therapeutic for corneal inflammatory diseases.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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