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Y. Momma, M.S. Chin, C.N. Nagineni, J.J. Hooks, B. Detrick; Antiviral actions of interferons in human retinal pigment epithelial cells: a model system to evaluate the potency of interferons in resident retinal cells . Invest. Ophthalmol. Vis. Sci. 2004;45(13):1642.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Viral infections are the frequent causes of retinal diseases that may result in sight threatening diseases especially in immunocompromised patients. In our previous studies, we have used human retinal pigment epithelial cultures (HRPE) to study the mechanisms of cytomegalovirus (CMV) replication and its prevention by antisense oligonucleotides. In this report, we evaluated the efficacy of interferons –α, ß, γ as anti–viral agents in HRPE. Methods: HRPE cultures were prepared from human donor eyes and human fibroblast cell line, MRC–5, was obtained from ATCC. CMV, Herpes Simplex Virus (HSV) and Vesicular Stomatitis Virus (VSV) were used for infection studies in HRPE and MRC–5 cells. The cell cultures were treated with human recombinant IFN–α, ß and γ for 24 h prior to inoculation of the cells with virus as well as throughout the viral replication cycle. Plaque assays were performed by methylcellulose overlay system. Results: A comparison of the potency of interferons (α,ß, γ) on CMV, HSV and VSV infectivity in HRPE cells revealed that all three types of interferons possessed high levels of antiviral activity. However, among the interferons, IFN–γ is the most potent anti–viral agent. Virus infected HRPE cells were as sensitive as MRC–5 cells to the antiviral infections of IFN–γ. A comparison of the potency of IFN–γ in HRPE cells against different viruses indicated that VSV was the most sensitive followed by CMV and HSV. For example, one unit of IFN–γ inhibited VSV by 97%, CMV by 85 % and HSV by 52%. Conclusions: This study demonstrates the usefulness of HRPE cells to evaluate the efficacy of antiviral agents in viral infections. HRPE, the cells that are infected with various types of herpes viruses during retinitis and retinal necrosis, is sensitive to anti–viral actions of IFN–α, ß and γ. Because of its most potent anti–viral activity, IFN–γ produced during acute viral retinopathies in man may play a primary protective role for resident cells during viral infection.
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