May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Non-Invasive Molecular Imaging of Selectin Ligands During Endotoxin-Induced Uveitis
Author Affiliations & Notes
  • F. Tayyari
    Ophthalmology, Massachusetts Eye and Ear Infirmary and Harvard Medical School, Boston, Massachusetts
  • S. Nakao
    Ophthalmology, Massachusetts Eye and Ear Infirmary and Harvard Medical School, Boston, Massachusetts
  • S. Zandi
    Ophthalmology, Massachusetts Eye and Ear Infirmary and Harvard Medical School, Boston, Massachusetts
  • L. Almulki
    Ophthalmology, Massachusetts Eye and Ear Infirmary and Harvard Medical School, Boston, Massachusetts
  • K. Noda
    Ophthalmology, Massachusetts Eye and Ear Infirmary and Harvard Medical School, Boston, Massachusetts
  • A. S. Schering
    Ophthalmology, Massachusetts Eye and Ear Infirmary and Harvard Medical School, Boston, Massachusetts
  • S. Frimmel
    Ophthalmology, Massachusetts Eye and Ear Infirmary and Harvard Medical School, Boston, Massachusetts
  • M. I. Melhorn
    Ophthalmology, Massachusetts Eye and Ear Infirmary and Harvard Medical School, Boston, Massachusetts
  • K. L. Thomas
    Ophthalmology, Massachusetts Eye and Ear Infirmary and Harvard Medical School, Boston, Massachusetts
  • A. Hafezi-Moghadam
    Ophthalmology, Massachusetts Eye and Ear Infirmary and Harvard Medical School, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  F. Tayyari, None; S. Nakao, None; S. Zandi, None; L. Almulki, None; K. Noda, None; A.S. Schering, None; S. Frimmel, None; M.I. Melhorn, None; K.L. Thomas, None; A. Hafezi-Moghadam, None.
  • Footnotes
    Support  NIH grant AI050775 to A.H.-M., NEI core grant EY14104, Massachusetts Lions Foundation and Research to Prevent Blindness
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 2864. doi:https://doi.org/
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    • Get Citation

      F. Tayyari, S. Nakao, S. Zandi, L. Almulki, K. Noda, A. S. Schering, S. Frimmel, M. I. Melhorn, K. L. Thomas, A. Hafezi-Moghadam; Non-Invasive Molecular Imaging of Selectin Ligands During Endotoxin-Induced Uveitis. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2864. doi: https://doi.org/.

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

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Abstract

Purpose: : Uveitis is a devastating inflammatory disease of uncertain etiology. L-selectin on the surface of leukocytes regulates leukocyte recruitment to inflammatory sites in many vascular beds, however, the role of L-selectin in the eye has not been studied. Utilizing our novel molecular imaging technique we target ligands of L-selectin on the choriocapillaris endothelium to study the role of these molecules during disease.

Methods: : Uveitis was induced in Lewis rats by footpad injection of LPS. Fluorescent microspheres were conjugated to protein G and incubated with recombinant L-selectin or mAbs against the L-selectin ligands, MAdCAM-1 or CD34 (1 µg/ml). Microspheres were injected systemically into anesthetized rats and their adhesion in the choriocapillaris were investigated under physiologic flow conditions by scanning laser ophthalmoscopy (SLO). Subsequently, animals were perfused and retinal and choroidal flatmounts were prepared to count the number of firmly adhering microspheres. MAdCAM-1 and CD34 were assessed by immunohistochemistry and western blot (WB). The spatial relationship of the microspheres with the choriocapillaris endothelium was visualized by confocal microscopy.

Results: : In normal animals only a few L-selectin conjugated microspheres firmly adhered in the choriocapillaris (202.4±16.2, n=5). In contrast, 4 h after LPS, a significantly higher number of microspheres adhered to the choriocapillaris (2380±140.6, n=5, p<0.01), suggesting an upregulation of the expression of L-selectin ligands during uveitis. The microsphere interaction flux 24 h post LPS remained significantly higher in EIU animals compared to normal controls (p<0.01). MAdCAM-1 was upregulated in EIU animals 24 and 72 h after LPS as detected by WB and immunohistochemistry. Confocal microscopy indicated that the microspheres in the choriocapillaris were attached to the endothelium.

Conclusions: : To study uveitis, we utilize a novel non-invasive method for detection of choroidal endothelial surface molecules. We characterize the expression of L-selectin ligands in the endothelium of choriocapillaris during EIU. Our novel molecular imaging approach allows quantitative assessment of endothelial injury. This technique could be further developed to detect subclinical signs of ocular inflammation.

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