The potential for mitochondrial therapeutics in the treatment of primary open-angle glaucoma: a review.

Glaucoma, an age-related neurodegenerative disease, is characterized by the death of retinal ganglion cells (RGCs) and the corresponding loss of visual fields. This disease is the leading cause of irreversible blindness worldwide, making early diagnosis and effective treatment paramount. The pathophysiology of primary open-angle glaucoma (POAG), the most common form of the disease, remains poorly understood. Current available treatments, which target elevated intraocular pressure (IOP), are not effective at slowing disease progression in approximately 30% of patients. There is a great need to identify and study treatment options that target other disease mechanisms and aid in neuroprotection for POAG. Increasingly, the role of mitochondrial injury in the development of POAG has become an emphasized area of research interest. Disruption in the function of mitochondria has been linked to problems with neurodevelopment and systemic diseases. Recent studies have shown an association between RGC death and damage to the cells' mitochondria. In particular, oxidative stress and disrupted oxidative phosphorylation dynamics have been linked to increased susceptibility of RGC mitochondria to secondary mechanical injury. Several mitochondria-targeted treatments for POAG have been suggested, including physical exercise, diet and nutrition, antioxidant supplementation, stem cell therapy, hypoxia exposure, gene therapy, mitochondrial transplantation, and light therapy. Studies have shown that mitochondrial therapeutics may have the potential to slow the progression of POAG by protecting against mitochondrial decline associated with age, genetic susceptibility, and other pathology. Further, these therapeutics may potentially target already present neuronal damage and symptom manifestations. In this review, the authors outline potential mitochondria-targeted treatment strategies and discuss their utility for use in POAG.

Genetic Factors Implicated in the Investigation of Possible Connections between Alzheimer's Disease and Primary Open Angle Glaucoma.

Both Alzheimer's disease (AD) and primary open angle glaucoma (POAG) are diseases of primary global neurodegeneration with complex pathophysiologies. Throughout the published literature, researchers have highlighted similarities associated with various aspects of both diseases. In light of the increasing number of findings reporting resemblance between the two neurodegenerative processes, scientists have grown interested in possible underlying connections between AD and POAG. In the search for explanations to fundamental mechanisms, a multitude of genes have been studied in each condition, with overlap in the genes of interest between AD and POAG. Greater understanding of genetic factors can drive the research process of identifying relationships and elucidating common pathways of disease. These connections can then be utilized to advance research as well as to generate new clinical applications. Notably, AD and glaucoma are currently diseases with irreversible consequences that often lack effective therapies. An established genetic connection between AD and POAG would serve as the basis for development of gene or pathway targeted strategies relevant to both diseases. Such a clinical application could be of immense benefit to researchers, clinicians, and patients alike. This paper aims to summarize the genetic associations between AD and POAG, describe common underlying mechanisms, discuss potential areas of application, and organize the findings in a review.

Paving the way while playing catch up: mitochondrial genetics in African ancestry primary open-angle glaucoma.

Glaucoma, the leading cause of irreversible blindness worldwide, disproportionately affects individuals of African descent. Specifically, previous research has indicated that primary open-angle glaucoma (POAG), the most common form of disease, is more prevalent, severe, early-onset, and rapidly-progressive in populations of African ancestry. Recent studies have identified genetic variations that may contribute to the greater burden of disease in this population. In particular, mitochondrial genetics has emerged as a profoundly influential factor in multiple neurodegenerative diseases, including POAG. Several hypotheses explaining the underlying mechanisms of mitochondrial genetic contribution to disease progression have been proposed, including nuclear-mitochondrial gene mismatch. Exploring the fundamentals of mitochondrial genetics and disease pathways within the understudied African ancestry population can lead to groundbreaking advancements in the research and clinical understanding of POAG. This article discusses the currently known involvements of mitochondrial genetic factors in POAG, recent directions of study, and potential future prospects in mitochondrial genetic studies in individuals of African descent.