Mitochondrial dysfunction and glaucoma.
Glaucoma is increasingly recognized as a neurodegenerative disorder, characterized by the accelerated loss of retinal ganglion cells (RGCs) and their axons. Open angle glaucoma prevalence and incidence increase exponentially with increasing age, yet the pathophysiology underlying increasing age as a risk factor for glaucoma is not well understood. Accumulating evidence points to age-related mitochondrial dysfunction playing a key role in the etiology of other neurodegenerative disorders including amyotrophic lateral sclerosis, Alzheimer and Parkinson disease. The 2 major functions of mitochondria are the generation of ATP through oxidative phosphorylation and the regulation of cell death by apoptosis. This review details evidence to support our hypothesis that age-associated mitochondrial dysfunction renders RGCs susceptible to glaucomatous injury by reducing the energy available for repair processes and predisposing RGCs to apoptosis. Eliciting the role of mitochondria in glaucoma pathogenesis may uncover novel therapeutic targets for protecting the optic nerve and preventing vision loss in glaucoma.
Kong
George Y X
GY
Centre for Eye Research Australia, University of Melbourne and Royal Victorian Eye and Ear Hospital, Australia.
Van Bergen
Nicole J
NJ
Trounce
Ian A
IA
Crowston
Jonathan G
JG
D000367:Age Factors; D000375:Aging / Q000502:physiology; D000818:Animals; D017209:Apoptosis; D001369:Axons / Q000378:metabolism / Q000648:ultrastructure; D004272:DNA, Mitochondrial / Q000032:analysis / Q000235:genetics; D005902:Glaucoma, Open-Angle / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D046529:Microscopy, Electron, Transmission; D028361:Mitochondrial Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009901:Optic Nerve Diseases / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D012165:Retinal Ganglion Cells / Q000378:metabolism* / Q000648:ultrastructure; D012307:Risk Factors
D004272:DNA, Mitochondrial