June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Treatment with repository corticotropin injection reduces the progression of experimental autoimmune uveitis in rats
Author Affiliations & Notes
  • Dale Wright
    Biological Sciences, Mallinckrodt Pharmaceuticals, Hazelwood, Missouri, United States
  • Ben Zweifel
    Biological Sciences, Mallinckrodt Pharmaceuticals, Hazelwood, Missouri, United States
  • Rick Fitch
    Biological Sciences, Mallinckrodt Pharmaceuticals, Hazelwood, Missouri, United States
  • Footnotes
    Commercial Relationships   Dale Wright, Mallinckrodt Pharmaceuticals (E); Ben Zweifel, Mallinckrodt Pharmaceuticals (E); Rick Fitch, Mallinckrodt Pharmaceuticals (E)
  • Footnotes
    Support  NONE
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 531. doi:
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      Dale Wright, Ben Zweifel, Rick Fitch; Treatment with repository corticotropin injection reduces the progression of experimental autoimmune uveitis in rats. Invest. Ophthalmol. Vis. Sci. 2017;58(8):531.

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

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Abstract

Purpose : Previous studies have suggested that melanocortin receptor (MCR) agonists play a role in regulating the progression and resolution of experimental autoimmune uveitis (EAU). Repository corticotropin injection (RCI: H.P. Acthar® gel) is a complex formulation containing a porcine ACTH analogue. ACTH is a melanocortin peptide that binds to the 5 known MCRs. Because RCI is an FDA-approved treatment for certain inflammatory ocular disorders, the aim of this study was to investigate the effects of RCI on a preclinical model EAU.

Methods : Lewis rats were immunized with interphotoreceptor retinoid binding protein (IRBP) peptide in complete Freud’s adjuvant. Inflammation was observed under a dissection microscope on days 4, 7, 11 and 14 post immunization and scored on a scale of 0-4 based on their anterior clinical disease. Animals were subcutaneously dosed with RCI (10, 40, or 400 U/kg), Placebo gel (5mL/kg) or Prednisolone (0.1, 1, or 5 mg/kg) every other day starting on the first day of the study. Sections were stained with hematoxylin & eosin and scored.

Results : Clinical assessment within the anterior chamber of the eye demonstrated that RCI administered at 40 or 400 U/kg significantly reduced the ocular clinical disease score on day 14 compared to placebo (0.93 ± 0.18 and 0.85 ± 0.17 versus 1.98 ± 0.22, respectively), (p≤ 0.01). In contrast, prednisolone marginally reduced the clinical disease score, at the doses tested, with only the 1 mg/kg dose having significance (1.05 ± 0.18; p ≤ 0.05). In addition, the clinical findings for RCI were supported by the histological data, showing protection to the retinal architecture with a reduction in inflammation at all 3 doses evaluated.

Conclusions : The treatment of EAU with RCI resulted in the suppression of the ocular clinical score and inflammation reducing retinal damage. These responses by RCI are thought to be through the different melanocortin receptors. While multiple melanocortin receptors have been shown to control inflammation, these data are the first to explore the effects of RCI in a preclinical model of experimental 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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