NDLI: Measurement of Systemic Mitochondrial Function in Advanced Primary Open-Angle Glaucoma and Leber Hereditary Optic Neuropathy

Content Provider	PubMed Central
Author	Bergen, Nicole J. Van Crowston, Jonathan G. Craig, Jamie E. Burdon, Kathryn P. Kearns, Lisa S. Sharma, Shiwani Hewitt, Alex W. Mackey, David A. Trounce, Ian A.
Editor	Demetrios, Vavvas
Copyright Year	2015
Abstract	Primary 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.
Related Links	http://dx.doi.org/10.1371/journal.pone.0140919
Starting Page	140919
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	10
Volume Number	10
Language	English
Publisher	Public Library of Science
Publisher Date	2015-10-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Data from: Measurement of systemic mitochondrial function in advanced primary open-angle glaucoma and Leber hereditary optic neuropathy (Dataset)

Rare Primary Mitochondrial DNA Mutations and Probable Synergistic Variants in Leber’s Hereditary Optic Neuropathy

Raised Intraocular Pressure as a Potential Risk Factor for Visual Loss in Leber Hereditary Optic Neuropathy

Mitochondrial DNA mutation m.10680G > A is associated with Leber hereditary optic neuropathy in Chinese patients

Mitochondrial Genome Analysis of Primary Open Angle Glaucoma Patients

Mitochondrial Sequence Variation in African-American Primary Open-Angle Glaucoma Patients

Mitochondrial Damage in the Trabecular Meshwork Occurs Only in Primary Open-Angle Glaucoma and in Pseudoexfoliative Glaucoma

Lamina Cribrosa Defects and Optic Disc Morphology in Primary Open Angle Glaucoma with High Myopia

Leber hereditary optic neuropathy and oxidative stress.

Measurement of Systemic Mitochondrial Function in Advanced Primary Open-Angle Glaucoma and Leber Hereditary Optic Neuropathy

Similar Documents

Data from: Measurement of systemic mitochondrial function in advanced primary open-angle glaucoma and Leber hereditary optic neuropathy (Dataset)

Rare Primary Mitochondrial DNA Mutations and Probable Synergistic Variants in Leber’s Hereditary Optic Neuropathy

Raised Intraocular Pressure as a Potential Risk Factor for Visual Loss in Leber Hereditary Optic Neuropathy

Mitochondrial DNA mutation m.10680G > A is associated with Leber hereditary optic neuropathy in Chinese patients

Mitochondrial Genome Analysis of Primary Open Angle Glaucoma Patients

Mitochondrial Sequence Variation in African-American Primary Open-Angle Glaucoma Patients

Mitochondrial Damage in the Trabecular Meshwork Occurs Only in Primary Open-Angle Glaucoma and in Pseudoexfoliative Glaucoma

Lamina Cribrosa Defects and Optic Disc Morphology in Primary Open Angle Glaucoma with High Myopia

Leber hereditary optic neuropathy and oxidative stress.

Measurement of Systemic Mitochondrial Function in Advanced Primary Open-Angle Glaucoma and Leber Hereditary Optic Neuropathy