| First Author | Berger S | Year | 2008 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 49 |
| Issue | 8 | Pages | 3605-10 |
| PubMed ID | 18660426 | Mgi Jnum | J:141980 |
| Mgi Id | MGI:3820151 | Doi | 10.1167/iovs.07-0817 |
| Citation | Berger S, et al. (2008) Deleterious role of TNF-alpha in retinal ischemia-reperfusion injury. Invest Ophthalmol Vis Sci 49(8):3605-10 |
| abstractText | PURPOSE: Tumor necrosis factor (TNF)-alpha is a mediator of neuronal cell death and survival in ischemia-reperfusion injury. This study was conducted to further elucidate the role of TNF-alpha and its receptor in an in vivo model of retinal ischemia-reperfusion injury by investigating its effects on retinal histopathology and function. METHODS: Retinal ischemia-reperfusion injury was performed on p55 and p75 knockout (KO) mice and Sprague-Dawley rats using the high intraocular pressure METHOD: The temporal expression of TNF-alpha was ascertained with immunohistochemical staining. Separate rats received intravitreal recombinant TNF-alpha or neutralizing antibody before or after ischemia. TUNEL labeling was performed to assess for cell death, and electroretinography was performed to assess function. RESULTS: TNF-alpha expression peaked at 12 to 24 hours after ischemia-reperfusion injury. TUNEL staining was diminished after intravitreal TNF-alpha antibody. Both transgenic KOs demonstrated significantly less functional impairment. Rats receiving recombinant TNF-alpha 48 hours after ischemia showed exaggerated functional impairment. Animals treated with TNF-alpha antibody before ischemia displayed significant functional improvement. CONCLUSIONS: TNF-alpha plays a largely deleterious role in ischemia-reperfusion injury in an in vivo model of retinal injury. Direct neutralization of this cytokine partially preserves retinal function. The diverse characteristics of TNF-alpha are attributed in part to the timing of its expression after injury. TNF-alpha receptor expression and function, along with combination treatments targeting death receptor-mediated apoptosis, should be further explored to develop neuroprotective therapeutic strategies for acute retinal ischemic disorders. |
