Despite more than 150 years of research, the precise biological mechanisms leading to glaucoma remain elusive. However, in the past decade, a theory related to mitochondrial dysfunction has come to the forefront of glaucoma research. This post will explore this intriguing aspect of glaucoma, guided by a study published in May 2023, and try to elucidate the role of mitochondria.
The Mighty Mitochondria and Glaucoma
Mitochondria, often referred to as the 'powerhouse of the cell,' are crucial for maintaining cell health. They generate ATP, the primary energy currency of cells, and participate in various vital cellular processes. When these organelles malfunction, nerve cells are among the first to be affected, leading, in the context of the eye, to glaucoma.
A key element of mitochondrial dysfunction is the overproduction of reactive oxygen species (ROS) from the mitochondrial respiratory chain. Normally, ROS are integral to cellular function and are efficiently neutralized by the cell's antioxidant system. However, when mitochondria falter, ROS production dramatically increases, causing oxidative stress - a state in which the cellular antioxidant system struggles to promptly eliminate these harmful molecules.
Unraveling the Mechanism
Mitochondrial dysfunction in glaucoma extends beyond oxidative stress. Research indicates that glaucoma shares several traits with mitochondrial impairment, including mitochondrial DNA (mtDNA) damage, defective mitochondrial quality control, and ATP reduction.
Damage to mtDNA and faulty mitochondrial quality control can lead to inefficient energy production and an accumulation of unhealthy mitochondria in cells. ATP reduction can impact various cellular activities since ATP is the primary energy source for cells. These alterations collectively contribute to glaucoma's onset and progression.
Lighting the Way Forward: Treatment Options
Given the substantial role of mitochondrial dysfunction in glaucoma, therapies targeting this issue offer a promising research avenue. Potential treatment methods under investigation include medications, exercise, red-light therapy, and dietary supplements, specifically vitamin B3 (as niacinamide) and BHB (beta-hydroxybutyrate). In my opinion, BHB is one of the most important mitochondria-focused antioxidants, as it functions at a crucial location in the mitochondria (Complex I) that most other antioxidants cannot effectively target.
Red-light therapy, a non-invasive treatment option, holds promise. This therapy uses specific wavelengths of red light to stimulate mitochondrial function. Studies suggest that it may help prevent retinal cell death and preserve vision in glaucoma patients. Some FitEyes members are currently evaluating the Eyepower Red glasses designed to stimulate mitochondrial function, and I eagerly await their feedback.
Exercise
In my opinion, a notable limitation of the current study is its failure to mention the well-documented role of exercise in supporting and enhancing mitochondrial health. Numerous studies show that exercise enhances mitochondrial function and is beneficial for people living with glaucoma. During physical activity, our body's energy demand increases, stimulating mitochondria to produce more ATP. This response triggers an increase in the number of mitochondria within our cells—termed mitochondrial biogenesis—especially in muscle cells.
Exercise is also known to enhance the efficiency of existing mitochondria and promote the removal and replacement of dysfunctional ones, a process known as mitophagy. Furthermore, exercise boosts the body's antioxidant defenses, thereby preventing ROS-induced damage. Therefore, in my view, regular moderate exercise could potentially alleviate mitochondrial dysfunction seen in glaucoma, enhance mitochondrial quality control, and reduce oxidative stress.
The connection between mitochondrial dysfunction and glaucoma presents a compelling area of research and paves the way for innovative therapeutic strategies, particularly lifestyle-based ones. Here is the abstract of the current study:
Abstract
Glaucoma is a kind of optic neuropathy primarily characterized by the permanent death of retinal ganglion cells (RGCs), atrophy of the optic nerve, and loss of visual ability. The main risk factors for glaucoma include 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 emerged in the last decade. Reactive oxygen species (ROS) from the mitochondrial respiratory chain are abnormally produced as a result of mitochondrial dysfunction. Oxidative stress occurs when the cellular antioxidant system fails to remove excessive ROS promptly. Concurrently, an increasing number of studies show that other common features of mitochondrial dysfunction in glaucoma, including damage to mitochondrial DNA (mtDNA), defective mitochondrial quality control, ATP reduction, and other cellular changes, 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 hold promise for providing feasible neuroprotective ideas for the treatment of glaucoma.
Keywords: glaucoma; mitochondrial dynamics; mitochondrial dysfunction; mitophagy; neuroprotection; oxidative stress.
- Mitochondrial dysfunction in glaucomatous degeneration - PubMed (https://pubmed.ncbi.nlm.nih.gov/37206187/)
- PMID: 37206187
- PMCID: PMC10172101 (http://www.ncbi.nlm.nih.gov/pmc/articles/pmc10172101/)
- DOI: 10.18240/ijo.2023.05.20 (https://doi.org/10.18240/ijo.2023.05.20)