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J. Zhou, M. Zhang, S.S. Atherton; Tumor Necrosis Factor Alpha (TNF–) Induced Apoptosis in MCMV Retinitis . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3064.
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© ARVO (1962-2015); The Authors (2016-present)
Murine cytomegalovirus (MCMV) infection in the BALB/c mouse eye induces apoptosis of nearby uninfected retinal cells, which, in turn, plays an important role in progression of MCMV retinitis. To explore the mechanism underlying the retinal apoptosis in MCMV retinitis, the aim of this study was to determine if the TNF receptor 1 (TNFR1) –TNF pathway was activated during MCMV retinitis.
The left eyes of immunosuppressed (IS) BALB/c mice were inoculated with MCMV k181 through superciliary injection. On days 3, 7, and 10 p.i., injected eyes were removed for RT–PCR for TNF–α and TNFR1. Protein expression of TNF–α, Caspase–8, and Caspase–3 was determined by staining frozen sections, Western blot, and quantitative ELISA. Apoptotic cells were identified by TUNEL labeling. All of the procedures were conducted on non–IS mice at the same time.
In IS mice, TNF–α and TNFR1 mRNA and protein expression were detected in MCMV infected eyes from day 3 after MCMV infection, with activation of Caspase–3 and Caspase–8. Most of the TNF–α expressing cells were MCMV infected RPE cells or macrophages derived from RPE cells. TNF–α co–localized with apoptotic retinal cells, and the level of this cytokine corresponded to the extent of the retinal pathology and to the number of apoptotic cells. In non–IS MCMV infected mice, TNF–α and TNFR1 expression appeared in the early stage of infection and disappeared by day 10 p.i.
The TNFR1–TNF pathway may be involved in induction of apoptosis and exacerbation of retinal pathology during MCMV retinitis. The observation that TNF–α and TNFR1 were present in both IS and non–IS mice suggests that TNF–α induced retinal apoptosis during MCMV infection is not T cell dependent.
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