Measurement of Systemic Mitochondrial Function in Advanced Primary Open-Angle Glaucoma and XXXX .

@entity1 @entity725 @entity66 @entity2479 @entity73 @entity726 @entity2790 @entity505 @entity179 @entity3649 @entity1781 @entity3054 @entity855
UNASSIGNED: @entity725 ( @entity725 ) is a common @entity179 characterized by the selective and gradual loss of @entity2479 cells (RGCs). Aging and @entity2790 (IOP) are @entity726 risk factors; nevertheless @entity1 deteriorate at all levels of IOP, implying other causative factors. Recent evidence presents mitochondrial oxidative phosphorylation (OXPHOS) complex-I impairments in @entity725 . @entity3054 ( @entity3054 ) @entity1 suffer specific and rapid loss of RGCs, predominantly in young adult males, due to complex-I mutations in the mitochondrial genome. This study directly compares the degree of @entity66 in @entity725 and @entity3054 @entity1 , testing the hypothesis that the milder clinical disease in @entity725 is due to a milder @entity73 . To assess overall mitochondrial capacity, cells can be forced to produce @entity855 primarily from mitochondrial OXPHOS by switching the media @entity505 source to @entity3649 . Under these conditions @entity725 lymphoblasts grew 1.47 times slower than controls, whilst @entity3054 demonstrated a greater degree of growth impairment (2.35 times slower). Complex-I enzyme specific activity was reduced by 18% in @entity725 lymphoblasts and by 29% in @entity3054 . We also assessed complex-I @entity855 synthesis, which was 19% decreased in @entity725 @entity1 and 17% decreased in @entity3054 @entity1 . This study demonstrates both @entity725 and @entity3054 have @entity73 , and in the majority of aspects the functional defects in @entity725 were milder than @entity3054 , which could reflect the milder disease development of @entity725 . This new evidence places @entity725 in the spectrum of mitochondrial @entity1781 and raises the possibility for new therapeutic targets aimed at improving mitochondrial function.
