Mitochondrial dysfunction in glaucomatous degeneration

Abstract

Glaucoma is a kind of optic neuropathy mainly manifested in the permanent death of retinal ganglion cells (RGCs), atrophy of the optic nerve, and loss of visual ability. The main risk factors for glaucoma consist of the pathological elevation of intraocular pressure (IOP) and aging. Although the mechanism of glaucoma remains an open question, a theory related to mitochondrial dysfunction has been emerging in the last decade. Reactive oxygen species (ROS) from the mitochondrial respiratory chain are abnormally produced as a result of mitochondrial dysfunction. Oxidative stress takes place when the cellular antioxidant system fails to remove excessive ROS promptly. Meanwhile, more and more studies show that there are other common features of mitochondrial dysfunction in glaucoma, including damage of mitochondrial DNA (mtDNA), defective mitochondrial quality control, ATP reduction, and other cellular changes, which are worth summarizing and further exploring. The purpose of this review is to explore mitochondrial dysfunction in the mechanism of glaucomatous optic neuropathy. Based on the mechanism, the existing therapeutic options are summarized, including medications, gene therapy, and red-light therapy, which are promising to provide feasible neuroprotective ideas for the treatment of glaucoma.

Functional implications of NHR-210 enrichment in C. elegans cephalic sheath glia: insights into metabolic and mitochondrial disruptions in Parkinson's disease models

“…The knockdown of pgp-9 not only disrupted mitochondrial homeostasis but also induced significant cellular apoptosis. This observation expands on the well-established concept of mitochondrial dysfunction leading to programmed cell death [ 51 – 55 ] and suggests that pgp-9 could be a pivotal player in the induction of mitochondrial-mediated apoptosis, a process implicated in neurodegeneration [ 56 – 58 ].…”

Immunomodulatory and Antioxidant Drugs in Glaucoma Treatment

“…Mitochondrial dysfunction plays a central pathophysiological role in glaucoma and is associated with inflammation, oxidative stress, impaired mitochondrial dynamics and reduced ATP production [ 104 ]. Excessive ROS and metabolic stress due to a nutrient deficit can lead to mtDNA mutations and subsequent mitochondrial dysfunction [ 105 ].…”

“…Excessive ROS and metabolic stress due to a nutrient deficit can lead to mtDNA mutations and subsequent mitochondrial dysfunction [ 105 ]. Mechanical insults from an elevated IOP can cause mitochondrial disruptions and deficiencies in the OPA1 gene, which regulates mitochondrial fusion, a process important for mitochondrial quality control [ 15 , 104 , 106 , 107 , 108 ]. A deficiency in OPA1 can trigger ROS overabundance and glutamate excitotoxicity [ 109 ].…”

The ketogenic diet and hypoxia promote mitophagy in the context of glaucoma

“…The neuroprotective effect of co-factors like NAD + and substrates like pyruvate directly connects mitochondrial function to the pathology of glaucoma. Oxidative stress through the generation of reactive oxygen species (ROS), mitochondrial DNA mutations ( Abu-Amero et al, 2006 ), and defective mitochondrial quality control mechanisms through IOP-induced fission and cristae depletion ( Ju et al, 2008 ) represent mitochondrial dysfunction that has been implicated in glaucoma ( Zhang et al, 2023 ). In light of this evidence, one avenue for glaucoma treatment could restore metabolic balance through maintenance of mitochondrial function.…”