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H. Chien, E. L. Blalock, C. L. Meier, R. D. Dix; Intraocular Tnf- Levels Increase During Progression of Experimental Cytomegalovirus Retinitis in Mice With Retrovirus-induced Immunosuppression. Invest. Ophthalmol. Vis. Sci. 2009;50(13):826.
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Invasion of the retina by human cytomegalovirus (HCMV) during HIV-1-induced immunosuppression results in retinal destruction to yield the classic histopathologic features of AIDS-related HCMV retinitis. Several mechanisms have been identified to account for this unique pattern of retinal tissue destruction that include virus-induced cytopathology and inflammation mediated by neutrophils and macrophages. We predict that additional mechanisms contribute to retinal tissue destruction, among them retinal necrosis mediated by TNF-. We therefore performed a series of experiments to test the hypothesis that intraocular TNF- levels increase during progression of experimental murine cytomegalovirus (MCMV) retinitis in mice with MAIDS, a clinically relevant animal model of retrovirus-induced immunosuppression.
Groups of C57BL/6 mice with MAIDS of 12-weeks duration were injected subretinally with MCMV or mock injected. At 3, 6, and 10 days postinfection, whole eyes were collected from all animal groups and subjected to real time RT-PCR assay for quantification of TNF- mRNA. Whole eyes from parallel groups of animals were analyzed histopathologically.
When compared with mock-injected eyes, MCMV-infected eyes of MAIDS animals at 3, 6, and 10 days postinfection exhibited 9-fold, 33-fold, and 3-fold increases in TNF- mRNA, respectively. Although progressive changes in retinal architecture were observed in MCMV-infected eyes recovered from mice with MAIDS at 3 and 6 days postinfection, frank retinal necrosis was not evident until 10 days postinfection.
Peak levels of TNF- mRNA preceded appearance of retinal necrosis in MCMV-infected eyes, and levels rapidly diminished thereafter upon development of retinal disease. We conclude that increased levels of TNF- within MCMV-infected eyes may indeed contribute to retinal tissue destruction observed during MAIDS-related MCMV retinitis.
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