XXXX -induced mitochondrial dysfunction in the retina.

@entity6 @entity2310 @entity3839 @entity989 @entity35 @entity4124 @entity224 @entity413
PURPOSE: Oxidative stress is increased in the retina in @entity6 , and antioxidants inhibit activation of @entity4124 and the development of @entity989 . The purpose of this study was to investigate the effect of @entity6 on the release of cytochrome c from mitochondria and translocation of @entity2310 into mitochondria in the @entity35 retina and in the isolated retinal capillary cells. METHODS: Mitochondria and cytosol fractions were prepared from retina of @entity35 with @entity3839 -induced @entity6 and from the isolated retinal endothelial cells and pericytes incubated in 5 or 20 mM @entity413 medium for up to 10 days in the presence of @entity224 dismutase (SOD) or a synthetic mimetic of SOD (MnTBAP). The release of cytochrome c into the cytosol and translocation of the proapoptotic protein @entity2310 into the mitochondria were determined by the Western blot technique and cell death by @entity4124 activity and ELISA assay. RESULTS: @entity6 of 8 months' duration in @entity35 increased the release of cytochrome c into the cytosol and @entity2310 into the mitochondria prepared from the retina, and this phenomenon was not observed at 2 months of @entity6 . Incubation of isolated retinal capillary cells with 20 mM @entity413 increased cytochrome c content in the cytosol and @entity2310 in the mitochondria, and these abnormalities were accompanied by increased cell apoptosis. Inclusion of SOD or its mimetic inhibited @entity413 -induced release of cytochrome c, translocation of @entity2310 , and apoptosis. CONCLUSIONS: Retinal mitochondria become leaky when the duration of @entity6 is such that capillary cell apoptosis can be observed; cytochrome c starts to accumulate in the cytosol and @entity2310 into the mitochondria. Inhibition of @entity224 inhibits @entity413 -induced release of cytochrome c and @entity2310 and inhibits apoptosis in both endothelial cells and pericytes. Identifying the mechanism by which retinal capillary cells undergo apoptosis may reveal novel therapies to inhibit the development of @entity989 in @entity6 .
