September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Therapeutic effect of topical treatment with everolimus-loaded nanocarriers in murine experimental autoimmune uveoretinitis (EAU).
Author Affiliations & Notes
  • Maren Kasper
    Department of Ophthalmology at St. Franziskus Hospital, Ophtha-Lab , Münster, Germany
  • Dirk Bauer
    Department of Ophthalmology at St. Franziskus Hospital, Ophtha-Lab , Münster, Germany
  • Lena Wildschuetz
    Department of Ophthalmology at St. Franziskus Hospital, Ophtha-Lab , Münster, Germany
  • Doris Gabriel
    Apidel SA, Geneva, Switzerland
  • Herve Courthion
    Apidel SA, Geneva, Switzerland
  • Michael Boehm
    University of Duisburg-Essen, Essen, Germany
  • Robert Gurny
    Apidel SA, Geneva, Switzerland
  • Michael Moeller
    University of Geneva, Geneva, Switzerland
  • Solon Thanos
    Institute for Experimental Ophthalmology, Westfalian-Wilhelms-University of Muenster, Muenster, Germany
  • Arnd Heiligenhaus
    Department of Ophthalmology at St. Franziskus Hospital, Ophtha-Lab , Münster, Germany
    University of Duisburg-Essen, Essen, Germany
  • Footnotes
    Commercial Relationships   Maren Kasper, None; Dirk Bauer, None; Lena Wildschuetz, None; Doris Gabriel, None; Herve Courthion , None; Michael Boehm, None; Robert Gurny, None; Michael Moeller, None; Solon Thanos, None; Arnd Heiligenhaus, None
  • Footnotes
    Support  Ernst und Berta Grimmke Foundation 5/13
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 1867. doi:
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      Maren Kasper, Dirk Bauer, Lena Wildschuetz, Doris Gabriel, Herve Courthion, Michael Boehm, Robert Gurny, Michael Moeller, Solon Thanos, Arnd Heiligenhaus; Therapeutic effect of topical treatment with everolimus-loaded nanocarriers in murine experimental autoimmune uveoretinitis (EAU).. Invest. Ophthalmol. Vis. Sci. 2016;57(12):1867.

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      © 2017 Association for Research in Vision and Ophthalmology.

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Abstract

Purpose : To investigate the effectivity of topically administered everolimus-loaded methoxy-poly-ethylene-glycol hexyl substituted poly-lactic acid (mPEGhexPLA) based micellar nanocarriers for the treatment of EAU.

Methods : EAU was induced in female B10.RIII mice (age 8 weeks) by immunization with human interphotoreceptor-retinoid-binding protein peptide 161-180 in complete Freunds adjuvant. Mice were treated five times per day starting on day 12 post immunization (p.i.) with 10µl of 0.5% everolimus-loaded mPEGhex-PLA micelles on the right eye (n=12) or PBS (n=12) as a control. Eyes, sera, cervical lymph nodes (LN) and spleens were collected on day 21 p.i.. The EAU-score was determined by histology. Antigen (Ag) or mitogen induced proliferation, cytokine secretion and frequency of FoxP3+ T-cells of isolated lymphocytes, and Ag-specific serum antibodies were determined via ELISA or flow-cytometry.

Results : Compared to PBS treated mice, unilateral topical everolimus treatment led to reduced EAU incidence (p<0.05) and severity (p<0.05) in both eyes. The treatment also resulted in reduced Ag-specific serum antibodies (p<0.05), mitogen-induced proliferation (p<0.05), and reduced IL-2-, IL-17-, and IFN-γ -secretion in the cells from the right cervical LN (p<0.05). Under everolimus treatment, the IL-10 secretion (p<0.05) and Treg frequency in cervical LN was enhanced compared to the PBS group. The cytokine secretion, proliferative response, and frequency of CD4+CD25+FoxP3+ regulatory splenocytes were not significantly altered.

Conclusions : Unilateral topical everolimus-loaded micelles improved EAU in both eyes. The effect is related to regional and also systemic immunomodulatory effects, as some systemic humoral and cellular immune responses are influenced.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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