April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Superior Sensitivity of Novel Molecular Imaging Probe: Simultaneously Targeting Two Types of Endothelial Injury Markers
Author Affiliations & Notes
  • D. Sun
    Ophthalmology, MEEI, Harvard Medical School, Boston, Massachusetts
  • S. Nakao
    Ophthalmology, MEEI, Harvard Medical School, Boston, Massachusetts
  • F. Xie
    Ophthalmology, MEEI, Harvard Medical School, Boston, Massachusetts
  • S. Zandi
    Ophthalmology, MEEI, Harvard Medical School, Boston, Massachusetts
  • A. Schering
    Ophthalmology, MEEI, Harvard Medical School, Boston, Massachusetts
  • J. Seraj
    Ophthalmology, MEEI, Harvard Medical School, Boston, Massachusetts
  • S. A. Frimmel
    Ophthalmology, MEEI, Harvard Medical School, Boston, Massachusetts
  • F. Faryan
    Ophthalmology, MEEI, Harvard Medical School, Boston, Massachusetts
  • A. Hafezi-Moghadam
    Ophthalmology, MEEI, Harvard Medical School, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  D. Sun, None; S. Nakao, None; F. Xie, None; S. Zandi, None; A. Schering, None; J. Seraj, None; S.A. Frimmel, None; F. Faryan, None; A. Hafezi-Moghadam, None.
  • Footnotes
    Support  NIH grants HL086933 and AI050775, Massachusetts Lions Eye Research Fund Inc., MPOB, and Research to Prevent Blindness.
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 1023. doi:
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    • Get Citation

      D. Sun, S. Nakao, F. Xie, S. Zandi, A. Schering, J. Seraj, S. A. Frimmel, F. Faryan, A. Hafezi-Moghadam; Superior Sensitivity of Novel Molecular Imaging Probe: Simultaneously Targeting Two Types of Endothelial Injury Markers. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1023.

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

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Abstract

Purpose: : There is an acute need for early diagnosis of ocular diseases. To detect endothelial injury at the early and reversible stage of adhesion molecule up-regulation, we generated novel imaging agents that target two distinct types of endothelial molecules, a mediator of rolling, P-selectin, and one that mediates firm adhesion, ICAM-1.

Methods: : Uveitis was induced in male Lewis rats (8-10 wks old) by injecting 100µg of lipopolysaccharide (LPS) into the footpad. Carboxylated fluorescent microspheres (MSs, 2µm) were covalently conjugated with mouse IgG, anti-Intercellular-Adhesion Molecule-1 (α-ICAM-1), recombinant P-selectin glycoprotein ligand-1 (rPSGL-1), or both. MSs (6x108) were injected into the tail vein of each animal. MS rolling in the fundus vessels was studied using a scanning laser ophthalmoscope (SLO, HRA2). 30min after MS injection, rats were perfused with PBS and rhodamine-labeled conA. Flatmounts were prepared for ex vivo evaluation of accumulated MS and leukocytes.

Results: : In normal animals (n=6), only very few conjugated MS rolled on the vascular endothelium of retinal or choroidal vessels. Double-conjugated MS adhered significantly more to the retinal vessels of EIU animals than IgG- (n=5, p=1.9×10-9), α-ICAM-1- (n=6, p=3×10-7), or rPSGL-1-conjugated MS (n=6, p=2.7×10-5), indicating increased levels of endothelial P-selectin and ICAM-1 expressions at these time points. In line with our SLO findings, flatmounts of double-conjugated MS in EIU animals showed significantly higher accumulation numbers in retinal and choroidal vessels than in normal controls (n=6; p<0.01).

Conclusions: : The present work introduces a novel imaging approach that advances our in vivo detection capabilities to the cellular and molecular level. Besides being a powerful research tool, this versatile imaging approach has a high chance of being translated to the clinical realm and impacting the way medicine is practiced.

Keywords: imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound) • uvea • inflammation 
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