Transgenic mice expressing IFN-γ in the retina develop inflammation of the eye and photoreceptor loss

K. Geiger, E. Howes, M. Gallina, Jian Huang Xiao Jian Huang, G. H. Travis, N. Sarvetnick

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

Purpose. Inflammatory mediators such as interferon-gamma (IFN-γ) are thought to play a role in ocular disease. Although IFN-γ was found in the vitreous of mice with experimentally induced autoimmune uveitis, intracameral injection of this cytokine did not induce intraocular inflammation in mice. Therefore, the authors created a transgenic mouse line using the rhodopsin promoter to direct the expression of IFN-γ in the photoreceptor cells of the retina. These mice, designated rhoγ, enabled them to model intraocular inflammatory disease. Methods. The authors fused a 2.1 kb 5' Hind III fragment from the murine rhodopsin gene to the IFN-γ gene and introduced the DNA construct into fertilized zygotes. These were implanted into pseudopregnant C57BL/6 mice, and the resulting progeny were crossed back to balb/c mice. The transgene was identified by Southern blot hybridization. Eyes from the rhoγ mice were either fixed in zinc formalin and stained with hematoxylin and eosin or were frozen in OCT compound and processed for immunostaining using the indirect immunoperoxidase method with DAB as a chromogen. Results. The rhoγ transgenic mice developed intraocular disease, manifested as intraocular cellular infiltration, loss of photoreceptors, corneal clouding, cataract formation, and epithelial and microglial proliferation. Additionally, rhoγ mice exhibited antigenic changes, comprising GFAP expression on Muller cells, accumulation of neurofilament on photoreceptors, and expression of MHC class I and class II molecules on retinal cells. Conclusions. IFN-γ alters the antigenic properties of intraocular tissue and induces intraocular inflammation in mice. The results suggest a key position of IFN-γ in the development of pathologic conditions related to intraocular inflammation and provide a useful animal model for the further study of inflammatory disorders, including autoimmune diseases.

Original languageEnglish (US)
Pages (from-to)2667-2681
Number of pages15
JournalInvestigative Ophthalmology and Visual Science
Volume35
Issue number6
Publication statusPublished - Jan 1 1994

    Fingerprint

Keywords

  • IFN-γ
  • MHC expression
  • intraocular inflammation
  • retina
  • transgenic mice

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this