May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
A Defect in Mitochondrial Complex I Induces ROS Release and Degeneration in Trabecular Meshwork Cells of POAG Patients: Protection by Antioxidants
Author Affiliations & Notes
  • Y. He
    Department of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Guangzhou, China
  • K. W. Leung
    Department of Neural and Behavioral Sciences, Pennsylvania State University College of Medicine, Hershey, Pennsylvania
  • Y. H. Zhang
    Department of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Guangzhou, China
  • S. Duan
    Department of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Guangzhou, China
  • J. Tombran-Tink
    Department of Neural and Behavioral Sciences, Pennsylvania State University College of Medicine, Hershey, Pennsylvania
    Department of Ophthalmology and Visual Science, Yale School of Medicine, New Haven, Connecticut
  • J. Ge
    Department of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Guangzhou, China
  • Footnotes
    Commercial Relationships  Y. He, None; K.W. Leung, None; Y.H. Zhang, None; S. Duan, None; J. Tombran-Tink, None; J. Ge, None.
  • Footnotes
    Support  National Basic Research Program of China (No. 2007CB512200);National Natural Science Foundation of China (No.30672275, No.30400486)
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 1626. doi:https://doi.org/
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      Y. He, K. W. Leung, Y. H. Zhang, S. Duan, J. Tombran-Tink, J. Ge; A Defect in Mitochondrial Complex I Induces ROS Release and Degeneration in Trabecular Meshwork Cells of POAG Patients: Protection by Antioxidants. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1626. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : There is growing evidence that oxidative stress contributes to the progression of primary open angle glaucoma (POAG), a leading cause of irreversible blindness worldwide. Here we provide evidence that mitochondrial dysfunction is a possible mechanism for loss of trabecular meshwork (TM) cells in individuals with POAG.

Methods: : TM from POAG (GTM) and age-matched non-diseased (NTM) individuals 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), thenoyltrifluoroacetone (TTFA, complex II inhibitor), myxothiazol or antimycin A (MYX, AM - complex III inhibitors); the mitochondrial permeability transition (MPT) inhibitor, cyclosporine A (CsA); the antioxidants, vitamin E (Vit E) or N-acetylcysteine (NAC). Mitochondrial function was determined by changes in mitochondrial membrane potential (ΔΨm) and ATP production, using 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 H2-DCF-DA, and cell death, measured by lactate dehydrogenase (LDH) activity and Annexin V-FITC labeling, were also examined.

Results: : GTM cells have higher endogenous ROS level, lower ATP level, decreased ΔΨm, and are more sensitive to mitochondrial complex I inhibition than their normal counterparts. ROT induces a further increase in ROS production, release of cytochrome c (cyt 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 cyt c release.

Conclusions: : We propose that a mitochondrial complex I defect is associated with degeneration of TM cells in POAG patients, and antioxidants and MPT inhibitors can reduce progression of this condition.

Keywords: trabecular meshwork • oxidation/oxidative or free radical damage • mitochondria 
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