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D. Hos, J. Onderka, F. Bock, B. Regenfuß, C. Cursiefen; Topical Antisense Oligonucleotide Eye Drops Against Insulin Receptor Substrate 1 Inhibit Inflammatory Corneal Lymphangiogenesis. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4947.
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© ARVO (1962-2015); The Authors (2016-present)
Lymphangiogenesis has been shown to be one of the most important risk-factors regarding graft rejection after corneal transplantation. Purpose of this study was to analyze whether GS-101 eye drops, an antisense oligonucleotide against insulin receptor substrate-1 (IRS-1), are able to inhibit inflammatory corneal lymphangiogenesis.
Inflammatory corneal neovascularization was induced by placing three interrupted 11-0 nylon sutures in the corneal stroma of 6 week old BALB/c mice. Four groups were treated with different concentrations of GS-101 eye drops (2x/day for one week, 5 microl per drop; 43, 86 and 172 microg/ml) or saline solution (15 mice per group). Afterwards, whole mounts of the corneas were prepared and stained with LYVE-1 as a lymphendothelial marker. The area covered with pathologic lymphatic vessels was detected by an algorithm on digitized fluorescence pictures using cell^F® software.
At a dose of 43 µg/ml, GS-101 eye drops showed not yet a significant inhibition of corneal lymphangiogenesis. When used at a dose of 86 µg/ml, corneal lymphangiogenesis was significantly inhibited by 21% (p<0.01), and the highest used dose (172 µg/ml) showed an even stronger inhibition (28% less, p<0.001) in comparison to control animals.
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