| First Author | Zhang M | Year | 2011 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 52 |
| Issue | 3 | Pages | 1800-8 |
| PubMed ID | 21310911 | Mgi Jnum | J:171518 |
| Mgi Id | MGI:4950313 | Doi | 10.1167/iovs.10-6904 |
| Citation | Zhang M, et al. (2011) Lack of TNF-alpha promotes caspase-3-independent apoptosis during murine cytomegalovirus retinitis. Invest Ophthalmol Vis Sci 52(3):1800-8 |
| abstractText | PURPOSE: Both caspase-dependent and caspase-independent apoptosis contribute to retinal damage during murine cytomegalovirus (MCMV) retinitis, and TNF-alpha is among the inducers of apoptosis. The aim of this study was to determine the contribution of TNF-alpha by studying virus replication and apoptosis in immunosuppressed (IS) TNF-alpha(-/-) mice. METHODS: IS TNF-alpha(-/-) mice or wild-type mice were inoculated with MCMV by the supraciliary route. Injected eyes were examined by plaque assay, electron microscopy, Western blot analysis (caspase-3, caspase-8, caspase-12, Bid, NF-kappaB, cFlip, XIAP), staining for MCMV early antigen, and TUNEL assay. RESULTS: Although the titer of MCMV was similar in both groups, significantly more apoptotic cells were observed in the retinas of IS TNF-alpha(-/-) mice than in those of wild-type mice. The level of active caspase-3 was similar in both groups; however, more activated proteins for genes involved in the mitochondrial pathway (cleaved caspase-8, tBid) and endoplasmic reticulum (ER) stress (cleaved caspase-12) and, though less active, NF-kappaB subunits and antiapoptotic proteins (XIAP and cFlip) were detected in the TNF-alpha(-/-) eyes compared with wild-type mice. CONCLUSIONS: Although TNF-alpha is an inducer of apoptosis, the results of this study suggest that TNF-alpha is also antiapoptotic by the following mechanism: TNF-alpha activation of NF-kappaB promotes the production of the antiapoptosis genes, c-flip or XIAP, which, in turn, inhibit the activation of caspase-8 and the mitochondrial pathway or the activation of caspase-12 and ER stress. |
