The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Mitochondrial Abnormalities in Patients with Primary Open-Angle Glaucoma
Abstract
PURPOSE: Primary open-angle glaucoma (POAG) is the second most common cause of blindness. It has been linked to mutations in the myocilin (MYOC) and optineurin (OPTN) genes, although mutations have been found in <5% of patients. The pathologic mechanism(s) of POAG remain unknown but may include retinal ganglion cell apoptosis, which causes progressive damage to axons at the optic nerve head. METHODS: In 27 patients with definite POAG, the MYOC and OPTN genes were sequenced, the entire mitochondrial (mt)DNA coding region was sequenced, relative mtDNA content was investigated, and mitochondrial respiratory function was assessed. RESULTS: Only three benign polymorphisms were identified in MYOC and OPTN in patients with POAG and in control subjects. Conversely, 27 different novel nonsynonymous mtDNA changes were found, only in patients with POAG (not control subjects), 22 of which (found in 14 patients) were potentially pathogenic. Unlike Leber hereditary optic neuropathy, most mtDNA sequence alterations in patients with POAG were transversions-sequence changes that alter the purine/pyrimidine orientation and imply oxidative stress. mtDNA content was relatively increased in 17 patients with POAG compared with age-matched control subjects, also implying a possible response to oxidative stress. Mean mitochondrial respiratory activity was decreased by 21% in patients with glaucoma compared with control subjects (P<0.001). CONCLUSIONS: These results reveal a spectrum of mitochondrial abnormalities in patients with POAG, implicating oxidative stress and implying that mitochondria dysfunction may be a risk factor for POAG. This concept may open up new experimental and therapeutic opportunities.
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Cites
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Quigley, H. A. (1996) · British Journal of Ophthalmology · doi:10.1136/bjo.80.5.389 · Cited by 2,998
Delettre, C., Lenaers, G., Griffoin, J.-M., Gigarel, N., Lorenzo, C., Belenguer, P., Pelloquin, L., Grosgeorge, J., Turc-Carel, C., Perret, E., et al. (2000) · Nature Genetics · doi:10.1038/79936 · Cited by 1,446
Alexander, C., Votruba, M., Pesch, U. E. A., Thiselton, D. L., Mayer, S., Moore, A., Rodriguez, M., Kellner, U., Leo-Kottler, B., Auburger, G., et al. (2000) · Nature Genetics · doi:10.1038/79944 · Cited by 1,330
Prediction of deleterious human alleles
Sunyaev, S. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.6.591 · Cited by 1,044
Mitochondrial dysfunction as a cause of optic neuropathies
Carelli, V., Ross-Cisneros, F. N., & Sadun, A. A. (2004) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2003.10.003 · Cited by 839
Quigley, H. A. (1999) · Progress in Retinal and Eye Research · doi:10.1016/s1350-9462(98)00014-7 · Cited by 790
Accounting for Human Polymorphisms Predicted to Affect Protein Function
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Mitochondrial biogenesis and mitochondrial DNA maintenance of mammalian cells under oxidative stress
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MITOMAP: a human mitochondrial genome database--2004 update
Brandon, M. C. (2004) · Nucleic Acids Research · doi:10.1093/nar/gki079 · Cited by 567
Analysis of Myocilin Mutations in 1703 Glaucoma Patients From Five Different Populations
Fingert, J. H., Heon, E., Liebmann, J. M., Yamamoto, T., Craig, J. E., Rait, J., Kawase, K., Hoh, S.-T., Buys, Y. M., Dickinson, J., et al. (1999) · Human Molecular Genetics · doi:10.1093/hmg/8.5.899 · Cited by 550
Cited by
Oxidative stress and mitochondrial dysfunction in glaucoma
Chrysostomou, V., Rezania, F., Trounce, I. A., & Crowston, J. G. (2013) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2012.09.008 · Cited by 403
Ito, Y. A., & Di Polo, A. (2017) · Mitochondrion · doi:10.1016/j.mito.2017.08.014 · Cited by 142
Glaucoma: Focus on mitochondria in relation to pathogenesis and neuroprotection
Osborne, N. N., Núñez-Álvarez, C., Joglar, B., & del Olmo-Aguado, S. (2016) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2016.04.032 · Cited by 101
Glaucoma as a Metabolic Optic Neuropathy: Making the Case for Nicotinamide Treatment in Glaucoma
Williams, P. A., Harder, J. M., & John, S. W. M. (2017) · Journal of Glaucoma · doi:10.1097/ijg.0000000000000767 · Cited by 102
PGC-1α signaling coordinates susceptibility to metabolic and oxidative injury in the inner retina
Guo, X., Dason, E. S., Zanon-Moreno, V., Jiang, Q., Nahirnyj, A., Chan, D., Flanagan, J. G., & Sivak, J. M. (2014) · The American Journal of Pathology · doi:10.1016/j.ajpath.2013.12.012 · Cited by 47
Metadata
- Authors
- Abu-Amero, K. K., Morales, J., & Bosley, T. M.
- Venue
- Investigative Opthalmology & Visual Science
- Published
- 2006-06-01
- Volume
- 47
- Issue
- 6
- Pages
- 2533
- ISSN
- 0146-0404 (ISSN-L)
- 1552-5783
- OpenAlex
- W2019853899
- Cited by
- 337
- References
- 30
- FWCI
- 12.04
- Type
- journal article
- Language
- en
- Open access
- closed
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