Mitochondrial Abnormalities in Patients with Primary Open-Angle Glaucoma

Abu-Amero, Khaled K.; Morales, José; Bosley, Thomas M.

doi:10.1167/iovs.05-1639

Cited by 288 publications

(256 citation statements)

References 43 publications

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“…9,22 Mitochondrial dysfunction and mtDNA defects have been implicated in RGC loss and the development of glaucoma. 7,10,22,23 The expansion of massively parallel sequencing has revolutionized mitochondrial genetics. [24][25][26] Sanger sequencing has long been considered the gold standard for molecular diagnosis of mtDNA-based disorders.…”

Section: Discussionmentioning

confidence: 99%

Whole-mitochondrial genome sequencing in primary open-angle glaucoma using massively parallel sequencing identifies novel and known pathogenic variants

Sundaresan

Simpson

Sambare

et al. 2015

Genetics in Medicine

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Section: Discussionmentioning

confidence: 99%

Whole-mitochondrial genome sequencing in primary open-angle glaucoma using massively parallel sequencing identifies novel and known pathogenic variants

Sundaresan

Simpson

Sambare

et al. 2015

Genetics in Medicine

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“…Several studies have shown that a maternal family history is more frequent than a paternal history in glaucoma [13-16] which suggests a contribution of mitochondrial DNA (mtDNA) to glaucoma pathogenesis. In fact, an increased frequency of nonsynonymous mtDNA sequence changes in patients with primary open angle glaucoma has been shown [17]. However, this report describes a relatively small number of patients from a restricted ethnic population and confirmation in other populations is still lacking.…”

Section: Introductionmentioning

confidence: 86%

“…A significant correlation between oxidative DNA damage in the trabecular meshwork and intraocular pressure (IOP) increase and visual field defects was observed in glaucomatous patients [10]. In an independent study, a significant reduction of mitochondrial respiratory function in peripheral blood cells was observed in glaucoma patients when compared to age-matched healthy controls [11]. Another study showed that the exposure of RGCs to elevated hydrostatic pressure resembling an elevated intraocular pressure results in altered mitochondrial fission [12].…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial haplogroup U is associated with a reduced risk to develop exfoliation glaucoma in the German population

Wolf

Gramer²,

Müller‐Myhsok

et al. 2010

BMC Genet

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BackgroundVarious lines of evidence demonstrate the involvement of mitochondrial dysfunction in the pathogenesis of glaucoma. Therefore, mitochondrial DNA is a promising candidate for genetic susceptibility studies on glaucoma. To test the hypothesis that mitochondrial haplogroups influence the risk to develop glaucoma, we genotyped 12 single-nucleotide polymorphisms that define the European mitochondrial DNA haplogroups in healthy controls and two German patient cohorts with either exfoliation glaucoma or the normal tension subgroup of primary open angle glaucoma.ResultsMitochondrial haplogroup U was significantly under-represented in patients with exfoliation glaucoma (8.3% compared with 18.9% in controls; p = 0.004).ConclusionsPeople with haplogroup U have a lower risk to develop exfoliation glaucoma. Our results substantiate the suggestion that mitochondrial alterations have an impact on the etiology of glaucoma.

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“…There is evidence of mitochondrial dysfunction in glaucoma (Mittag et al, 2000;Tatton et al, 2001;Tezel and Yang, 2004); and as summarized in section 3, mitochondrial dysfunction critically participates in RGC death (Tezel and Yang, 2004). By demonstrating mitochondrial DNA abnormalities, a recent study also implicates mitochondrial dysfunction-associated oxidative stress as a risk factor for glaucoma patients (Abu-Amero et al, 2006). In addition to somal death, mitochondrial dysfunction likely contributes to compartmentalized neurodegenerative processes in glaucoma.…”

Section: Oxidative Stress In Widespread Damage To Rgcs In Glaucomamentioning

confidence: 99%

Oxidative stress in glaucomatous neurodegeneration: Mechanisms and consequences

Tezel

2006

Progress in Retinal and Eye Research

612

449

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Reactive oxygen species (ROS) are generated as by-products of cellular metabolism, primarily in the mitochondria. Although ROS are essential participants in cell signaling and regulation, when their cellular production overwhelms the intrinsic antioxidant capacity, damage to cellular macromolecules such as DNA, proteins, and lipids ensues. Such a state of "oxidative stress" is thought to contribute to the pathogenesis of a number of neurodegenerative diseases. Growing evidence supports the involvement of oxidative stress as a common component of glaucomatous neurodegeneration in different subcellular compartments of retinal ganglion cells (RGCs). Besides the evidence of direct cytotoxic consequences leading to RGC death, it also seems highly possible that ROS are involved in signaling RGC death by acting as a second messenger and/or modulating protein function by redox modifications of downstream effectors through enzymatic oxidation of specific amino acid residues. Different studies provide cumulating evidence, which supports the association of ROS with different aspects of the neurodegenerative process. Oxidative protein modifications during glaucomatous neurodegeneration increase neuronal susceptibility to damage and also lead to glial dysfunction. Oxidative stress-induced dysfunction of glial cells may contribute to spreading neuronal damage by secondary degeneration. Oxidative stress also promotes the accumulation of advanced glycation end products in glaucomatous tissues. It is also evident that oxidative stress takes part in the activation of immune response during glaucomatous neurodegeneration, as ROS stimulate the antigen presenting ability of glial cells and also function as co-stimulatory molecules during antigen presentation. By discussing current evidence, this review provides a broad perspective on cellular mechanisms and potential consequences of oxidative stress in glaucoma.

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Mitochondrial Abnormalities in Patients with Primary Open-Angle Glaucoma

Abstract: 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.

Cited by 288 publications

References 43 publications

Whole-mitochondrial genome sequencing in primary open-angle glaucoma using massively parallel sequencing identifies novel and known pathogenic variants

Whole-mitochondrial genome sequencing in primary open-angle glaucoma using massively parallel sequencing identifies novel and known pathogenic variants

Mitochondrial haplogroup U is associated with a reduced risk to develop exfoliation glaucoma in the German population

Oxidative stress in glaucomatous neurodegeneration: Mechanisms and consequences

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