May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
In vivo Imaging of Endothelial Injury in the Choriocapillaris During Endotoxin-Induced Uveitis
Author Affiliations & Notes
  • A. Hafezi-Moghadam
    Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • S. Miyahara
    Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • L. Almulki
    Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • K. Noda
    Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • T. Nakazawa
    Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • T. Hisatomi
    Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • K. L. Thomas
    Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • J. W. Miller
    Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • S. Masli
    Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • E. S. Gragoudas
    Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • Footnotes
    Commercial Relationships A. Hafezi-Moghadam, R-Tech Ueno, Ltd., F; S. Miyahara, None; L. Almulki, None; K. Noda, None; T. Nakazawa, None; T. Hisatomi, None; K.L. Thomas, None; J.W. Miller, None; S. Masli, None; E.S. Gragoudas, None.
  • Footnotes
    Support R-Tech Ueno, NIH grant AI050775 to A.H.M., NEI core grant EY14104, Massachusetts Lions Foundation, and Research to Prevent Blindness
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 3450. doi:
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    • Get Citation

      A. Hafezi-Moghadam, S. Miyahara, L. Almulki, K. Noda, T. Nakazawa, T. Hisatomi, K. L. Thomas, J. W. Miller, S. Masli, E. S. Gragoudas; In vivo Imaging of Endothelial Injury in the Choriocapillaris During Endotoxin-Induced Uveitis. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3450.

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

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Abstract

Purpose:: Early diagnosis of ocular inflammation may prevent vision loss. Therefore, clinical outcomes could be improved, if inflammation could be detected prior to structural damage. We aim to develop a non-invasive technique for molecular imaging of endothelial injury in the choroidal vessels of live animals.

Methods:: Rats were injected with 100µg of LPS to cause endotoxin-induced uveitis (EIU). Recombinant P-selectin glycoprotein ligand-1 immunoglobulin (YSPSL, Y's Therapeutics, Inc.) was conjugated to fluorescent microspheres (2µm diam.), and PSGL-1 site densities were determined by flow cytometry. Microspheres were injected systemically into anesthetized rats, and their rolling and adhesion in the choroidal vessels were investigated under physiologic flow by scanning laser ophthalmoscopy (SLO). Furthermore, the expression of P-selectin in the choroidal vessels was measured by reverse transcription-PCR at different time points after LPS.

Results:: YSPSL conjugated microspheres rolled (4±1) and firmly adhered (14±1) to the choroidal endothelium in normal animals (n=6) at baseline levels, resembling constitutive leukocyte endothelial interaction. However, in EIU animals the rolling numbers significantly increased, with a peak 4-10h after LPS (13±2, n=6, P<0.01). Similarly, the adhesion numbers peaked at 4h after LPS in the temporal areas of the choroidal microcirculation (9.5-fold, 133±10, n=6, P<0.01), while there was a biphasic peak at 4h (6.9-fold, P<0.01) and 36h (5.5-fold, P<0.01) after LPS around the optic disk. Consistent with our functional data, choroidal P-selectin mRNA expression in these animals peaked at 4 and 36h after LPS.

Conclusions:: We introduce a novel non-invasive method for detection of choroidal endothelial surface antigens in vivo, allowing quantitative assessment of endothelial injury. Though the bio-safety of these microspheres in humans is currently unknown, this technique could be further developed to diagnose subclinical signs of ocular inflammatory diseases such as diabetic retinopathy, uveitis, or AMD.

Keywords: vascular cells • imaging/image analysis: non-clinical • choroid 
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