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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)
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.
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.
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).
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.
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