Oxidative stress and mitochondrial dysfunction in glaucoma

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

“…14,15 Mitochondria may contribute to their own accelerated DNA mutational rate during periods of localized environmental stress; mitochondria both generate and act as a target for excessive reactive oxygen species from altered oxidative phosphorylation. 9 Several mtDNA variants can exist within a cell or tissue, a situation termed heteroplasmy. New mtDNA mutations can coexist at a low frequency with wildtype mtDNAs, making it challenging to identify all mutations in the mitochondrial genome.…”

“…2 Given the high metabolic demands of RGCs, they are heavily dependent on mitochondrial function for their function and survival. 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.…”

“…5,6 Mitochondrial abnormalities are associated with a number of optic neuropathies, 5,6 and there is evidence that mitochondrial DNA (mtDNA) defects and dysfunction play a role in POAG. [7][8][9][10][11][12] Mitochondrial genetic variants have also been linked to other neurodegenerative diseases, including Parkinson disease, Alzheimer disease, and Friedreich ataxia. 13 The mitochondrial genome is organized as a circular, doublestranded DNA molecule in the mitochondrion and codes for only 37 genes across ~16,600 base pairs.…”

Dynamic, in vivo, real-time detection of retinal oxidative status in a model of elevated intraocular pressure using a novel, reversibly responsive, profluorescent nitroxide probe

“…The rat retinal I/R model, which mimics clinical situations such as retinal vascular occlusion disease and acute glaucoma, is an established animal model for studying retinal cell responses after an ischemic insult (Cho et al, 2011;Sun et al, 2010). It is believed that impairment of mitochondrial integrity is a key factor in ROS-mediated neurodegeneration (Chrysostomou et al, 2013;Osborne and del Olmo-Aguado, 2013).…”

Multipronged Approach to Study Glaucoma-Associated Phenotypes

“…Recent evidence shows that mitochondrial dysfunction is present in some glaucoma patients. POAG patients have been reported to have increased levels of mtDNA mutations as well as deficiencies in complex-I driven ATP synthesis and respiration (233). Although evidence of mitochondrial dysfunction was reported in patients with glaucoma, there is no direct evidence that mitochondrial dysfunction contributes to the pathogenesis of glaucoma.…”