Show simple item record

dc.contributor.authorVan Bergen, Nicole J
dc.contributor.authorCrowston, Jonathan G
dc.contributor.authorCraig, Jamie E
dc.contributor.authorBurdon, Kathryn Penelope
dc.contributor.authorKearns, Lisa S
dc.contributor.authorSharma, Shiwani
dc.contributor.authorHewitt, Alex W
dc.contributor.authorTrounce, Ian A
dc.date.accessioned2016-05-27T00:37:22Z
dc.date.available2016-05-27T00:37:22Z
dc.date.issued2015
dc.identifier.citationVan Bergen NJ, Crowston JG, Craig JE, Burdon KP, Kearns LS, Sharma S, et al. (2015) Measurement of Systemic Mitochondrial Function in Advanced Primary Open-Angle Glaucoma and Leber Hereditary Optic Neuropathy. PLoS ONE 10(10): e0140919. doi:10.1371/journal.pone.0140919en
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/2328/36130
dc.description.abstractPrimary Open Angle Glaucoma (POAG) is a common neurodegenerative disease characterized by the selective and gradual loss of retinal ganglion cells (RGCs). Aging and increased intraocular pressure (IOP) are glaucoma risk factors; nevertheless patients deteriorate at all levels of IOP, implying other causative factors. Recent evidence presents mitochondrial oxidative phosphorylation (OXPHOS) complex-I impairments in POAG. Leber Hereditary Optic Neuropathy (LHON) patients 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 OXPHOS impairment in POAG and LHON patients, testing the hypothesis that the milder clinical disease in POAG is due to a milder complex-I impairment. To assess overall mitochondrial capacity, cells can be forced to produce ATP primarily from mitochondrial OXPHOS by switching the media carbon source to galactose. Under these conditions POAG lymphoblasts grew 1.47 times slower than controls, whilst LHON lymphoblasts demonstrated a greater degree of growth impairment (2.35 times slower). Complex-I enzyme specific activity was reduced by 18% in POAG lymphoblasts and by 29% in LHON lymphoblasts. We also assessed complex-I ATP synthesis, which was 19% decreased in POAG patients and 17% decreased in LHON patients. This study demonstrates both POAG and LHON lymphoblasts have impaired complex-I, and in the majority of aspects the functional defects in POAG were milder than LHON, which could reflect the milder disease development of POAG. This new evidence places POAG in the spectrum of mitochondrial optic neuropathies and raises the possibility for new therapeutic targets aimed at improving mitochondrial function.en
dc.language.isoen
dc.publisherPublic Library of Scienceen
dc.relationhttp://purl.org/au-research/grants/NHMRC/529915en
dc.relationhttp://purl.org/au-research/grants/NHMRC/529923en
dc.relationhttp://purl.org/au-research/grants/NHMRC/590200en
dc.relationhttp://purl.org/au-research/grants/NHMRC/590225en
dc.relationhttp://purl.org/au-research/grants/NHMRC/1061472en
dc.rightsCopyright © 2015 Van Bergen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.titleMeasurement of Systemic Mitochondrial Function in Advanced Primary Open-Angle Glaucoma and Leber Hereditary Optic Neuropathyen
dc.typeArticleen
dc.relation.grantnumberNHMRC/529915en
dc.relation.grantnumberNHMRC/529923en
dc.relation.grantnumberNHMRC/590200en
dc.relation.grantnumberNHMRC/590225en
dc.relation.grantnumberNHMRC/1061472en
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0140919en
dc.rights.holderThe Authorsen


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record