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M.A. Fields, N.M. Archin, M. Zheng, S.S. Atherton; The Role of Tumor Necrosis Factor-Alpha (TNF-) in the Eyes and Brain of HSV-1 Infected BALB/c Mice . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4633.
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Purpose: Following uniocular anterior chamber (AC) inoculation of HSV-1, virus spreads to the suprachiasmatic nuclei (SCN) and at day 5 p.i., TNF-α is detected in this area. The objective of these studies was to determine if blocking TNF-α affects the timing or amount of virus spread after AC inoculation of HSV-1. Methods: On day 0, 9.3 × 104 PFU of the KOS strain of HSV-1 was injected into the AC of euthymic BALB/c mice. Experimental mice were injected intraperitoneally with 200 mg/kg-1 of pentoxifylline (PENT), an inhibitor of TNF-α, diluted in PBS on days –1- +4 or with 100 mg/kg-1 of thalidomide (THAL), another inhibitor of TNF-α, diluted in PBS and DMSO on days –1- +4. Control mice were injected intraperitoneally with an equivalent amount of PENT or THAL diluent and then with virus via AC route. All mice were sacrificed on day 5 post-inoculation, and the brain and eyes were removed. Immunohistochemistry and immunofluorescence were used to determine the presence of HSV-1 in the SCN and both eyes, and the amount of virus in the injected eye and SCN was determined by plaque assay. Results: In the brain, only the ipsilateral SCN of control mice was virus positive whereas both the ipsilateral and contralateral SCN were infected in mice treated with PENT or THAL. The titer of virus in the SCN was slightly increased in treated mice compared with controls (Avg: 1.62 × 103 PFU vs. 4.61 × 102 PFU). The number of infected cells in the anterior segment was equivalent in experimental and control mice. In the posterior segment of the injected eye, the number of HSV-1 infected cells was increased in THAL or PENT treated mice and the virus titer was slightly increased compared with controls (Avg: 1.75 × 105 PFU vs. 6.89 × 104 PFU). Conclusions: The results suggest that TNF-α plays a role in limiting virus spread from the SCN to the retina of the injected eye and/or from the anterior to the posterior segment of the injected eye.
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