April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
Topical Antisense Oligonucleotide Eye Drops Against Insulin Receptor Substrate 1 Inhibit Inflammatory Corneal Lymphangiogenesis
Author Affiliations & Notes
  • D. Hos
    Department of Ophthalmology, University of Erlangen-Nuremberg, Nuremberg, Germany
  • J. Onderka
    Department of Ophthalmology, University of Erlangen-Nuremberg, Erlangen, Germany
  • F. Bock
    Department of Ophthalmology, University of Erlangen-Nuremberg, Erlangen, Germany
  • B. Regenfuß
    Department of Ophthalmology, University of Erlangen-Nuremberg, Erlangen, Germany
  • C. Cursiefen
    Department of Ophthalmology, University of Erlangen-Nuremberg, Erlangen, Germany
  • Footnotes
    Commercial Relationships  D. Hos, None; J. Onderka, None; F. Bock, None; B. Regenfuß, None; C. Cursiefen, None.
  • Footnotes
    Support  Interdisciplinary Center for Clinical Research (IZKF) Erlangen (A9); German Research Foundation: SFB 643 (B10)
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 4947. doi:https://doi.org/
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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. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : 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.

Methods: : 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.

Results: : 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.

Keywords: neovascularization • inflammation • drug toxicity/drug effects 
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