April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Effective Treatment Of Experimental Autoimmune Uveitis With Everolimus Is Associated With The Support Of Regulatory T-cells
Maren Hennig; Dirk Bauer; Martin Busch; Susanne Wasmuth; Karoline Walscheid; Solon Thanos; Arnd Heiligenhaus
Author Affiliations & Notes
  • Maren Hennig
    Dept. of Ophthalmology and Ophtha Lab at St. Franziskus Hospital, Muenster, Germany
    Dept. of Ophthalmology, University of Duisburg-Essen, Essen, Germany
  • Dirk Bauer
    Dept. of Ophthalmology and Ophtha Lab at St. Franziskus Hospital, Muenster, Germany
  • Martin Busch
    Dept. of Ophthalmology and Ophtha Lab at St. Franziskus Hospital, Muenster, Germany
  • Susanne Wasmuth
    Dept. of Ophthalmology and Ophtha Lab at St. Franziskus Hospital, Muenster, Germany
  • Karoline Walscheid
    Dept. of Ophthalmology and Ophtha Lab at St. Franziskus Hospital, Muenster, Germany
  • Solon Thanos
    Institute of Experimental Ophthalmology, School of Medicine, University Muenster, Muenster, Germany
  • Arnd Heiligenhaus
    Dept. of Ophthalmology and Ophtha Lab at St. Franziskus Hospital, Muenster, Germany
    Dept. of Ophthalmology, University of Duisburg-Essen, Essen, Germany
  • Footnotes
    Commercial Relationships  Maren Hennig, Supported in part by Novartis (F); Dirk Bauer, None; Martin Busch, None; Susanne Wasmuth, None; Karoline Walscheid, None; Solon Thanos, None; Arnd Heiligenhaus, Supported in part by Novartis (F)
  • Footnotes
    Support  DFG-BA 2248/1-1
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 2276. doi:
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      Maren Hennig, Dirk Bauer, Martin Busch, Susanne Wasmuth, Karoline Walscheid, Solon Thanos, Arnd Heiligenhaus; Effective Treatment Of Experimental Autoimmune Uveitis With Everolimus Is Associated With The Support Of Regulatory T-cells. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2276.

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Abstract

Purpose: : To study the efficacy and the action mechanism of everolimus for the treatment of experimental autoimmune uveitis (EAU).

Methods: : EAU was induced in B10.RIII mice by immunization with interphotoreceptor retinoid-binding protein peptide 161-180 (IRBP). Mice were daily treated therapeutically (day 14-21 post immunization, n=19) with everolimus (5mg/kg in 5% glucose) by oral administration. Control mice received equivalent volumes of 5% glucose without drug (n=20). The eyes were analyzed histopathologically. Lymphocyte proliferation ([3H]-thymidine test) and delayed type hypersensitivity (DTH) were measured. IL-2, IL-6 and IL-17 levels were studied intraocularly (Bead-Array) and in cell-culture supernatants from splenocytes (ELISA). Additionally the presence of IRBP-specific serum-antibodies was tested (ELISA). Regulatory T-cells were studied in peripheral blood, lymph nodes, and spleen by flow-cytometry. The suppressive efficiency of splenic CD4+CD25+ T-cells of everolimus treated and untreated mice were analyzed in a suppression assay.

Results: : The EAU incidence and severity, and the DTH of everolimus treated immunized mice were significantly reduced. Splenocytes of everolimus treated mice had decreased proliferative response. Moreover IL-2, IL-6 and IL-17 secretion in the eyes and spleen, and IRBP-specific serum-antibody content were reduced. Everolimus treated mice had increased CD4+CD25+Foxp3+ cell numbers in the spleen. In contrast to CD4+CD25+ splenocytes of untreated mice, the cells from the everolimus treated mice suppressed the antigen specific proliferation of CD4+CD25- effector T-cells.

Conclusions: : Uveitis improvement with everolimus was associated with a reduced IRBP-specific effector-cell-response, and an increased frequency of CD4+CD25+Foxp3+ T-cells with an enhanced suppressive efficiency on IRBP-specific effector-T-cells.

Keywords: uveitis-clinical/animal model • autoimmune disease • drug toxicity/drug effects 
© 2011, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2024 Association for Research in Vision and Ophthalmology.
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