June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Systemic administration of an anti-IL-6R antibody mitigated visual decline in a murine model of Experimental Autoimmune Uveitis (EAU)
Author Affiliations & Notes
  • Nazia Mushfiqa Alam
    Burke Medical Research Institute, White Plains, New York, United States
  • Glen T Prusky
    Burke Medical Research Institute, White Plains, New York, United States
    Physiology and Biophysics, Weill Cornell Medical College, New York, New York, United States
  • Thomas Clayton MacPherson
    Regeneron Pharmaceuticals, Inc, Tarrytown, New York, United States
  • Jingtai Cao
    Regeneron Pharmaceuticals, Inc, Tarrytown, New York, United States
  • Stanley J Wiegand
    Regeneron Pharmaceuticals, Inc, Tarrytown, New York, United States
  • George Yancopoulos
    Regeneron Pharmaceuticals, Inc, Tarrytown, New York, United States
  • Carl Romano
    Regeneron Pharmaceuticals, Inc, Tarrytown, New York, United States
  • Footnotes
    Commercial Relationships   Nazia Alam, CerebralMechanics, Inc (E); Glen Prusky, CerebralMechanics Inc (P); Thomas MacPherson, Regeneron Pharmaceuticals, Inc (E); Jingtai Cao, Regeneron Pharmaceuticals, Inc (E); Stanley Wiegand, Regeneron Pharmaceuticals, Inc (E); George Yancopoulos, Regeneron Pharmaceuticals, Inc (E); Carl Romano, Regeneron Pharmaceuticals, Inc (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 537. doi:
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      Nazia Mushfiqa Alam, Glen T Prusky, Thomas Clayton MacPherson, Jingtai Cao, Stanley J Wiegand, George Yancopoulos, Carl Romano; Systemic administration of an anti-IL-6R antibody mitigated visual decline in a murine model of Experimental Autoimmune Uveitis (EAU). Invest. Ophthalmol. Vis. Sci. 2017;58(8):537.

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

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Abstract

Purpose : Uveitis is a major source of human visual disability. Previous studies demonstrated that a murine IL-6R antibody delivered systemically inhibits the retinal and choroidal inflammation and reduces infiltrates in the vitreous in C57BL/6 mice (Cao et al, IOVS 2013; E-Abstract 5193). The present study aimed to determine if visual function (i.e. spatial frequency and contrast thresholds) declined with EAU and if so, to determine if anti-IL6R treatment would mitigate the decline.

Methods : Experimental autoimmune uveitis (EAU) was induced in male C57BL/6 mice (8-10 weeks old) using immunization with human interphotoreceptor retinal-binding protein (IRBP) peptide (New England Peptide), mycobacterium tuberculosis (Difco) in Complete Freund’s adjuvant, and pertussis toxin (Sigma). Spatial visual thresholds were measured in the mice with a virtual optokinetic system (OptoMotry, CerebralMechanics Inc.), and a fundus evaluation was obtained weekly. In Study-1, visual function was measured at baseline and during the course of EAU. Spatial frequency and contrast thresholds in both eyes were measured, and the baseline results were consistent with published values for normal C57BL/6 mice (Prusky et al, 2004; 2006). In Study-2, Animals in EAU groups, were intraperitoneally injected with either an active anti-IL-6R antagonists (anti-mIL-6R, 100 mg/kg) or control protein (mFc, 33mg/kg) every 3 days from days 5 post EAU. Animals were terminated on day 28 to collect ocular tissues for histology analysis.

Results : We found that visual decline commenced in the uveitis group within 2 weeks of EAU induction, and reached ~40% after 4 weeks. No visual decline was found in non-immunized controls. Visual decline was mitigated in Anti-IL-6R antibody-treated groups: decline was delayed until 3 weeks after induction. In EAU animals treated with with mFc the decline was unchanged. Improved visual function was accompanied by improved fundus scores.

Conclusions : These data indicate that systemic administration of an anti-IL-6R antibody may hold promise to treat autoimmune uveitis.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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