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F. Xie, D. Sun, A. Schering, S. Nakao, S. Zandi, A. Hafezi-Moghadam; In vivo Molecular Imaging of Endothelial Injury in Iris Vasculature. Invest. Ophthalmol. Vis. Sci. 2010;51(13):6364.
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Acute anterior uveitis is the most common form of uveitis. Early detection of vascular injury would allow effective treatments that could halt inflammation before irreversible structural damages occur. The close proximity of the well-perfused iris vessels to the light-permeable cornea make iris an ideal tissue for non-invasive molecular imaging.
Iritis was induced in male Lewis rats (8-10 wks old) by injecting 100µg of lipopolysaccharide (LPS) into one hind footpad of each animal. Carboxylated fluorescent microspheres (MS, 2µm) were covalently conjugated with mouse IgG or recombinant P-selectin glycoprotein ligand-1 (rPSGL-1) and systemically injected (6x108) into the tail vein. MS adhesion in the iris was studied by intravital microscopy. Rats were perfused with PBS and rhodamine-labeled conA. Subsequently, flatmounts were prepared for ex vivo evaluation.
To detect earliest signs of iritis in living animals, we performed intravital microscopy using our rPSGL-1-conjugated imaging agents. In normal animals, 30min after MS injection, a low number of control (38.8±7.1, n=5) or rPSGL-1-conjugated (41.6±17.1, n=5; p=0.9) MSs interacted with the iris endothelium. In LPS-treated animals, significantly higher numbers of rPSGL-1-conjugated MS (223.3±44.5) bound to the endothelium than control MS (116±19.8; p=0.03). Iris flatmounts confirmed specific adhesion of the MSs in the iridal vessels. Topical treatment with Dex (n=6, p=0.0003) or CsA (n=6, p=0.005) significantly lowered MS interaction in the iris compared to vehicle-treated controls (217.3±24.6, n=5).
This work introduces quantitative assessment of endothelial injury in the iris vasculature. Molecular imaging of the iris provides a unique opportunity for quantifying the immune response in vivo, due to its accessibility and direct involvement in ocular diseases. Besides being a powerful research tool, this versatile imaging approach has a high chance of being translated to the clinical realm.
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