December 2002
Volume 43, Issue 13
Free
ARVO Annual Meeting Abstract  |   December 2002
The TNF-alpha Inhibitor Enbrel Reduces Leukocyte Adhesion, Vascular Leakage and Apoptotic Cell Death in Endotoxin Induced Uveitis In Vivo
Author Affiliations & Notes
  • K Koizumi
    Department for Vitreoretinal Surgery University Eye Clinic Cologne Cologne Germany
  • S Doehmen
    Department for Vitreoretinal Surgery University Eye Clinic Cologne Cologne Germany
  • G Welsandt
    Department for Vitreoretinal Surgery University Eye Clinic Cologne Cologne Germany
  • B Kirchhof
    Department for Vitreoretinal Surgery University Eye Clinic Cologne Cologne Germany
  • V Poulaki
    Massachusetts Eye and Ear Infirmary Harvard Medical School Boston MA
  • AM Joussen
    Department for Vitreoretinal Surgery University Eye Clinic Cologne Cologne Germany
  • Footnotes
    Commercial Relationships   K. Koizumi, None; S. Doehmen, None; G. Welsandt, None; B. Kirchhof, None; V. Poulaki, None; A.M. Joussen, None.
Investigative Ophthalmology & Visual Science December 2002, Vol.43, 1557. doi:
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    • Get Citation

      K Koizumi, S Doehmen, G Welsandt, B Kirchhof, V Poulaki, AM Joussen; The TNF-alpha Inhibitor Enbrel Reduces Leukocyte Adhesion, Vascular Leakage and Apoptotic Cell Death in Endotoxin Induced Uveitis In Vivo . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1557.

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

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Abstract

Abstract: : Purpose:To investigate the effect of systemic injections of the TNF-alpha inhibitor Enbrel on the development of endotoxin-induced uveitis (EIU) in the rat. Methods:EIU was induced in Long Evans rats by a single footpad injection of lipopolysaccharide (LPS; 350 microg/kg) from Salmonella typhimurium. Rats were treated with a subcutaneous injection in the back of recombinant TNF receptor P75 (Enbrel) 24h before LPS injection. At 24 hours after LPS injection, Leukocyte adhesion was evaluated with SLO-Acridine Orange Fluography in vivo, Concanavalin A lectin staining in the flat mounted retina and quantified by myeloperoxidase activity assay. Vascular leakage was assessed by Evans blue extravasation. Retinal cell death was assayed in quantifying DNA fragmentation in the retina. Results:At 24 hours after LPS injection, significant clinical inhibition of ocular inflammation and fibrin deposition in the eye was observed in Enbrel-treated rats. Quantitative analysis of vascular leakage revealed a significant decrease after treatment with Enbrel. Retinal cell death quantification showed a significant decrease after treatment with the TNF-alpha-inhibitor. Conclusion:Anti-TNF-alpha treatment inhibits LPS-induced ocular inflammation with inhibition of vascular leakage in the eye. Enbrel might be useful in the treatment of autoimmune-uveitis.

Keywords: 612 uveitis-clinical/animal model • 423 growth factors/growth factor receptors • 390 drug toxicity/drug effects 
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