April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
In-vivo imaging of choroidal neovascularization using a fluorescent labeled multivalent polymer targeting L- and P-selectin
Author Affiliations & Notes
  • Johanna Meyer
    Department of Ophthalmology, University of Bonn, Bonn, Germany
  • Dagmar Sonntag-Bensch
    Department of Ophthalmology, University of Bonn, Bonn, Germany
  • Pia Welker
    Mivenion GmbH, Berlin, Germany
  • Kai Licha
    Mivenion GmbH, Berlin, Germany
  • Jens Dernedde
    Zentralinstitut für Labormedizin und Pathobiochemie, Charité-Universitätsmedizin Berlin, Berlin, Germany
  • Rainer Haag
    Institute of Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany
  • Steffen Schmitz-Valckenberg
    Department of Ophthalmology, University of Bonn, Bonn, Germany
  • Frank G Holz
    Department of Ophthalmology, University of Bonn, Bonn, Germany
  • Footnotes
    Commercial Relationships Johanna Meyer, Carl-Zeiss Meditc AG (F), Heidelberg Engineering (F); Dagmar Sonntag-Bensch, Carl Zeiss Meditec AG (F), Heidelberg Engineering (F); Pia Welker, Mivenion GmbH (E); Kai Licha, Mivenion GmbH (E); Jens Dernedde, None; Rainer Haag, None; Steffen Schmitz-Valckenberg, Heidelberg Engineering (F), Heidelberg Engineering (R), Optos (F), Optos (R), ZeissMeditec (F); Frank Holz, Acucela (C), Acucela (F), Allergan (C), Allergan (F), Bayer (C), Bayer (F), Boehringer Ingelheim (C), Carl Zeiss (F), Genentech (C), Genentech (F), Heidelberg Engineering (C), Heidelberg Engineering (F), Merz (F), Novartis (C), Novartis (F), Optos (F), Roche (C)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 1952. doi:https://doi.org/
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      Johanna Meyer, Dagmar Sonntag-Bensch, Pia Welker, Kai Licha, Jens Dernedde, Rainer Haag, Steffen Schmitz-Valckenberg, Frank G Holz; In-vivo imaging of choroidal neovascularization using a fluorescent labeled multivalent polymer targeting L- and P-selectin. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1952. doi: https://doi.org/.

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

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Abstract

Purpose: Selectins are expressed on the vascular endothelium and leukocytes, mediating the migration of leukocytes during inflammation. The novel multivalent synthetic dendritic polyglycerol sulfate (dPGS) inhibits selectins and suppresses inflammation. Aim of the study was to investigate fluorescently labeled dPGS as imaging probe in an animal model of laser-induced choroidal neovascularization (CNV).

Methods: For in-vivo imaging, dPGS was covalently attached to an indocyanine green type dye (6S-ICG), yielding soluble conjugates. Using confocal scanning laser ophthalmoscopy (cSLO), in-vivo reflectance and fluorescence imaging was performed in Dark Agouti rats that had undergone argon laser photocoagulation to induce CNV. Retinal uptake and fluorescence were recorded following intravenous and intravitreal injection of dPGS-6S-ICG. The distribution and accumulation of dPGS-6S-ICG were measured and frozen sections as well as flatmounts were prepared.

Results: Immediately following intravenous and intravitreal injection a strong fluorescence was visible. Twenty-four hours following injection an accumulation of dPGS-6S-ICG within the laser lesions were observed. Furthermore, multiple fluorescent spots were visible up to 56 days following intravenous injection and for up to 100 days following intravitreal injection of dPGS-6S-ICG. Over time, a continuous decrease of the fluorescence intensity was observed. Post-mortem analysis revealed a distinct accumulation to macrophages and/or microglia cells in frozen sections (after staining with CD68 and Iba1).

Conclusions: Pharmacokinetics of fluorescent dPGS can be investigated in-vivo following intravenous and intravitreal injection. The in-vivo and ex-vivo observations are in accordance with an immune mediated response following laser treatment. Fluorescent dPGS may be a potential biomarker for the in-vivo assessment of inflammation and leukocyte migration in retinal disorders.

Keywords: 453 choroid: neovascularization • 552 imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound) • 688 retina  
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