Effect of an intravitreal cyclosporine implant on experimental uveitis in horses

Brian C. Gilger, Emily Malok, Tammy Stewart, David Horohov, Paul Ashton, Thomas Smith, Glenn J. Jaffe, Janice B. Allen

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

The purpose of this study was to determine the effects of an intravitreal device releasing cyclosporine A (CsA) on recurrent inflammatory episodes in experimental uveitis. Nine normal horses were immunized peripherally with H37RA-mTB antigen twice, and then received 25μg of H37RA-mTB antigen intravitreally in the right eye and an equal volume of balanced salt solution intravitreally in the left eye. Two weeks later, the animals randomly received either a CsA or a polymer implant (without CsA) in both eyes 1 week following implantation of the devices, 25μg of H37RA-mTB antigen was reinjected into the right eye of each animal. Clinical signs of ophthalmic inflammation were graded following injections and implantation. The animals from each group were euthanized at 3, 14, and 28 days following the second injection. Aqueous and vitreous humor protein concentrations were measured. The presence, number, and type (CD4, 5 and 8) of infiltrating inflammatory cells and amount of tissue destruction were determined. Total RNA was isolated and quantitative reverse transcriptase-polymerase chain reaction was performed for equine specific interleukin (IL) 2 and 4, interferon-gamma (IFNγ) and beta-actin. In addition, aqueous and vitreous humor and peripheral blood were collected at the termination of the experiments and analyzed for CsA concentration by HPLC. Within 4h of the first intravitreal H37RA-mTB antigen injection, each animal developed epiphora, blepharospasm, mild corneal edema, aqueous flare, myosis, and vitreous opacity. The severity of signs peaked 48 to 72h after injection and subsequently decreased back to normal within 14 days. Following the second injection, clinical signs in the eyes with the CsA device were less severe and significantly shorter in duration than signs with the polymer only implant eyes. Aqueous and vitreous humor protein levels, infiltrating cell numbers, total number of T-lymphocytes, and levels of IL-2 and IFNγ-mRNA were significantly less in eyes with the CsA implant compared to eyes with the polymer only. CsA implants did not completely eliminate the development of a second ('recurrent') experimental inflammatory episode in these horses. However, the duration and severity of inflammation, cellular infiltration, tissue destruction, and pro-inflammatory cytokines RNA transcript levels were significantly less in those eyes implanted with the CsA device. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)239-255
Number of pages17
JournalVeterinary Immunology and Immunopathology
Volume76
Issue number3-4
DOIs
StatePublished - Oct 31 2000

Bibliographical note

Funding Information:
The authors would like to acknowledge the technical assistance provided by Arden Bond, Duncan Morgan, Jennifer Friemann, Katherine Cutter, and Chad Vanderhayden. This work was supported in part by the State of North Carolina, the Veterinary Equine Research Center Foundation, grants #EY11364 (JA), EY09106 (GJ), and 5P30EY05722 (Duke Core) from the NEI, the Louisiana State University Equine Veterinary Research Program (DH), and the Grayson Jockey Club Research Foundation, Inc. (DH).

Keywords

  • Cyclosporine
  • Equine
  • Experimental
  • Intravitreal
  • Uveitis

ASJC Scopus subject areas

  • Immunology
  • Veterinary (all)

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