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Article: Mitochondrial complex i defect induces ROS release and degeneration in trabecular meshwork cells of POAG patients: Protection by antioxidants

TitleMitochondrial complex i defect induces ROS release and degeneration in trabecular meshwork cells of POAG patients: Protection by antioxidants
Authors
Issue Date2008
PublisherAssociation for Research in Vision and Ophthalmology. The Journal's web site is located at http://www.iovs.org
Citation
Investigative Ophthalmology And Visual Science, 2008, v. 49 n. 4, p. 1447-1458 How to Cite?
AbstractPurpose. There is growing evidence that oxidative stress contributes to the progression of primary open-angle glaucoma (POAG), a leading cause of irreversible blindness worldwide. The authors provide evidence that mitochondrial dysfunction is a possible mechanism for the loss of trabecular meshwork (TM) cells in persons with POAG. Methods. TM from patients with POAG (GTM) and age-matched subjects without disease (NTM) were obtained by standard surgical trabeculectomy. Primary TM cultures were treated with one of the following mitochondrial respiratory chain inhibitors: rotenone (ROT, complex I inhibitor), thenoyl-trifluoroacetone (TTFA, complex II inhibitor), myxothiazol or antimycin A (MYX, AM-complex III inhibitors); mitochondrial permeability transition (MPT) inhibitor cyclosporine A (CsA); and antioxidants vitamin E (Vit E) or N-acetylcysteine (NAC). Mitochondrial function was determined by changes in mito-chondrial membrane potential (δψm) and adenosine triphosphate (ATP) production with the fluorescent probes 5,5′6,6′ tetrachloro-1,1′ 3,3′-tetraethylbenzimid azolocarbocyanine iodide (JC-1) and a luciferin/luciferase-based ATP assay, respectively. Reactive oxygen species (ROS) level, determined by H 2-DCF-DA, and cell death' measured by lactate dehydrogenase activity and Annexin V-FITC labeling, were also examined. Results. GTM cells have higher endogenous ROS levels, lower ATP levels, and decreased Aψm and they are more sensitive to mitochondrial complex I inhibition than their normal counterparts. ROT induces a further increase in ROS production, the release of cytochrome c and decreases in ATP level and δψm in GTM cells, eventually leading to apoptosis. Complex II and III inhibition had little effect on the cells. Antioxidants protect against ROT-induced death by inhibiting ROS generation and cytochrome c release. Conclusions. The authors propose that a mitochondrial complex I defect is associated with the degeneration of TM cells in patients with POAG, and antioxidants and MPT inhibitors can reduce the progression of this condition. Copyright © Association for Research in Vision and Ophthalmology.
Persistent Identifierhttp://hdl.handle.net/10722/169853
ISSN
2015 Impact Factor: 3.427
2015 SCImago Journal Rankings: 2.008
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorHe, Yen_HK
dc.contributor.authorLeung, KWen_HK
dc.contributor.authorZhang, YHen_HK
dc.contributor.authorDuan, Sen_HK
dc.contributor.authorZhong, XFen_HK
dc.contributor.authorJiang, RZen_HK
dc.contributor.authorPeng, Zen_HK
dc.contributor.authorTombranTink, Jen_HK
dc.contributor.authorGe, Jen_HK
dc.date.accessioned2012-10-25T04:57:05Z-
dc.date.available2012-10-25T04:57:05Z-
dc.date.issued2008en_HK
dc.identifier.citationInvestigative Ophthalmology And Visual Science, 2008, v. 49 n. 4, p. 1447-1458en_HK
dc.identifier.issn0146-0404en_HK
dc.identifier.urihttp://hdl.handle.net/10722/169853-
dc.description.abstractPurpose. There is growing evidence that oxidative stress contributes to the progression of primary open-angle glaucoma (POAG), a leading cause of irreversible blindness worldwide. The authors provide evidence that mitochondrial dysfunction is a possible mechanism for the loss of trabecular meshwork (TM) cells in persons with POAG. Methods. TM from patients with POAG (GTM) and age-matched subjects without disease (NTM) were obtained by standard surgical trabeculectomy. Primary TM cultures were treated with one of the following mitochondrial respiratory chain inhibitors: rotenone (ROT, complex I inhibitor), thenoyl-trifluoroacetone (TTFA, complex II inhibitor), myxothiazol or antimycin A (MYX, AM-complex III inhibitors); mitochondrial permeability transition (MPT) inhibitor cyclosporine A (CsA); and antioxidants vitamin E (Vit E) or N-acetylcysteine (NAC). Mitochondrial function was determined by changes in mito-chondrial membrane potential (δψm) and adenosine triphosphate (ATP) production with the fluorescent probes 5,5′6,6′ tetrachloro-1,1′ 3,3′-tetraethylbenzimid azolocarbocyanine iodide (JC-1) and a luciferin/luciferase-based ATP assay, respectively. Reactive oxygen species (ROS) level, determined by H 2-DCF-DA, and cell death' measured by lactate dehydrogenase activity and Annexin V-FITC labeling, were also examined. Results. GTM cells have higher endogenous ROS levels, lower ATP levels, and decreased Aψm and they are more sensitive to mitochondrial complex I inhibition than their normal counterparts. ROT induces a further increase in ROS production, the release of cytochrome c and decreases in ATP level and δψm in GTM cells, eventually leading to apoptosis. Complex II and III inhibition had little effect on the cells. Antioxidants protect against ROT-induced death by inhibiting ROS generation and cytochrome c release. Conclusions. The authors propose that a mitochondrial complex I defect is associated with the degeneration of TM cells in patients with POAG, and antioxidants and MPT inhibitors can reduce the progression of this condition. Copyright © Association for Research in Vision and Ophthalmology.en_HK
dc.languageengen_US
dc.publisherAssociation for Research in Vision and Ophthalmology. The Journal's web site is located at http://www.iovs.orgen_HK
dc.relation.ispartofInvestigative Ophthalmology and Visual Scienceen_HK
dc.titleMitochondrial complex i defect induces ROS release and degeneration in trabecular meshwork cells of POAG patients: Protection by antioxidantsen_HK
dc.typeArticleen_HK
dc.identifier.emailLeung, KW: kwleung1@hku.hken_HK
dc.identifier.authorityLeung, KW=rp01674en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1167/iovs.07-1361en_HK
dc.identifier.pmid18385062-
dc.identifier.scopuseid_2-s2.0-45549087104en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-45549087104&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume49en_HK
dc.identifier.issue4en_HK
dc.identifier.spage1447en_HK
dc.identifier.epage1458en_HK
dc.identifier.isiWOS:000254577200024-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridHe, Y=7404942872en_HK
dc.identifier.scopusauthoridLeung, KW=13106059300en_HK
dc.identifier.scopusauthoridZhang, YH=8571439000en_HK
dc.identifier.scopusauthoridDuan, S=7102434797en_HK
dc.identifier.scopusauthoridZhong, XF=7202160588en_HK
dc.identifier.scopusauthoridJiang, RZ=8246183800en_HK
dc.identifier.scopusauthoridPeng, Z=8882451200en_HK
dc.identifier.scopusauthoridTombranTink, J=7003724753en_HK
dc.identifier.scopusauthoridGe, J=25421653600en_HK

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