Investigative Ophthalmology & Visual Science, Vol 35, 332-341, Copyright © 1994 by Association for Research in Vision and Ophthalmology

ARTICLES AND REPORTS

Ectopic expression of gamma interferon in the eyes of transgenic mice induces ocular pathology and MHC class II gene expression

CE Egwuagu, J Sztein, CC Chan, W Reid, R Mahdi, RB Nussenblatt and AB Chepelinsky
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892.

PURPOSE. To direct the expression of gamma IFN to the eyes of transgenic mice as a means of investigating the possible role of this lymphokine in ocular pathogenesis. METHODS. Transgenic mouse strains were generated by injection of a DNA fragment containing the murine alpha A-crystallin promoter fused to the coding sequence of murine gamma IFN gene. PCR and RT-PCR were used to screen for the presence of the transgene and mRNA analyses, respectively. Methacrylate-embedded eye sections were analyzed for morphology and cryosections for immunoperoxidase antibody staining. RESULTS. The most notable effects of gamma IFN in these transgenic mice include cataract, microphthalmia, blepharophimosis, microphakia, impairment of lens fiber formation, arrest of retinal differentiation, serous retinal detachment with presence of macrophages in the subretinal space, persistent hyperplastic primary vitreous, and corneal vascularization. MHC class II mRNA levels were significantly increased in the transgenic eyes and MHC class II proteins were expressed in their cornea, iris, ciliary body, choroid, lens and RPE. CONCLUSIONS. Ectopic expression of gamma IFN in the lens affected the growth of the whole eye, resulting in microphthalmia and microphakia. The author's data suggest that alpha ACry-gamma IFN transgenic mouse ocular cells express functional gamma IFN receptors and that interaction of gamma IFN with its receptor induced biochemical and morphologic changes in the transgenic eyes. These mice provide an animal model for the study of the linkage between aberrant MHC expression and predisposition to autoimmune diseases.

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