| First Author | Barakat DJ | Year | 2012 |
| Journal | J Neurochem | Volume | 120 |
| Issue | 4 | Pages | 586-97 |
| PubMed ID | 22118627 | Mgi Jnum | J:182276 |
| Mgi Id | MGI:5315087 | Doi | 10.1111/j.1471-4159.2011.07595.x |
| Citation | Barakat DJ, et al. (2012) Astroglial NF-kappaB mediates oxidative stress by regulation of NADPH oxidase in a model of retinal ischemia reperfusion injury. J Neurochem 120(4):586-97 |
| abstractText | Astrocytes undergo rapid activation after injury, which is mediated in part by the transcription factor nuclear factor-kappaB (NF-kappaB). Consequently, activated astrocytes have been shown to induce the NF-kappaB regulated phagocyte NADPH oxidase (PHOX), resulting in elevated production of reactive oxygen species. We investigated the regulatory mechanisms of PHOX-induced oxidative stress in astrocytes and its non-cell-autonomous effects on retinal ganglion cell loss following retinal ischemia-reperfusion (IR) injury. To study PHOX activity and neurotoxicity mediated by glial NF-kappaB, we employed GFAP-IkappaBalpha-dn transgenic mice, where the NF-kappaB canonical pathway is suppressed specifically in astrocytes. Our analysis showed that NF-kappaB activation in astrocytes correlated with an increased expression of PHOX and reactive oxygen species production in primary cells and whole retinas subjected to oxygen-glucose deprivation or IR injury. Selective blockade of NF-kappaB in astrocytes or application of NADPH oxidase inhibitors suppressed retinal ganglion cell loss in co-cultures with astroglia challenged by oxygen-glucose deprivation. Furthermore, genetic suppression of astroglial NF-kappaB reduced oxidative stress in ganglion layer neurons in vivo in retinal IR. Collectively, our results suggest that astroglial NF-kappaB-regulated PHOX activity is a crucial toxicity pathway in the pathogenesis of retinal IR injury. |
