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Jeremy M. Sivak, Xiaoxin Guo; Involvement of PGC-1α Signaling in Retinal Astrocyte Activation and Ganglion Cell Damage. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4604.
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The multi-faceted etiology of glaucoma converges at the optic nerve head (ONH), where metabolic dysfunction and ischemic damage can result in apoptotic death of retinal ganglion cells (RGCs). A candidate pathway that may integrate these responses is the recently identified transcriptional co-activator, PGC-1α (peroxisome proliferator-activated receptor gamma co-activator). In response to oxidative, metabolic, and hypoxic stress, PGC-1α binds to and co-activates various transcription factors to mediate key cellular responses in skeletal muscle, liver, and brain. We have investigated the role of PGC-1α and its signaling pathway in the adult retina, and in mouse models of ganglion cell damage.
Localization and concentrations of PGC-1α and pathway proteins were measured in mouse retinas by immunofluorescence microscopy and Western blotting. Results were compared to the co-staining patterns of established retinal cell markers. Changes in these parameters were measured in ischemia and toxin-induced mouse models of RGC damage and compared to markers of cellular damage and apoptosis.
PGC-1α protein was highly localized to retinal astrocytes, but was absent from Muller glial cells, RGCs, and other retinal layers. Concentrations of PGC-1α and associated proteins were increased after RGC damage.
The specific astrocyte localization and damage-induced changes to PGC-1α signaling suggest its role in mediating responses to metabolic and oxidative stress in the retina. Further investigation of PGC-1α signaling may reveal an important new pathway modulating RGC damage responses.
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