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

Abstract

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.

Effects and potential mechanisms of exercise and physical activity on eye health and ocular diseases

“…These mitochondria are primarily located in the myelin-free axons of RGCs and the inner segments of photoreceptors, fulfilling a crucial role in normal energy transportation (140). Mitochondrial dysfunction, potentially caused by various mechanisms such as dysregulation of signaling, dysfunction of pathways, genetic variations, and oxidative stress, is significantly associated with a majority of blinding eye conditions, including glaucoma (141,142). The mitochondria in the RGCs are the first to be affected by glaucoma (143).…”

“…Furthermore, the expression of OPA 1, a gene that is present in RGCs soma and axons and linked to both spontaneous and hereditary mitochondrial optic neuropathy, exhibits noteworthy down-regulation in patients identified with POAG, providing evidence of a genetic association connecting mitochondrial function and POAG (144). Mitochondrial abnormalities in morphology, reduced mass, decreased oxidative capacity, and abnormal autophagy, among other factors, can all contribute to glaucoma development (142).…”

Mitophagy in Astrocytes Is Required for the Health of Optic Nerve

“…Mitochondrial dysfunction is linked to various ocular diseases, including autosomal dominant optic atrophy [85], Leber's hereditary optic neuropathy [86], glaucoma [87], age-related macular degeneration (AMD) [88], and diabetic retinopathy (DR) [89]. It is known that inflammation can be triggered by oxidative stress caused by mitochondrial damage [90].…”

Effects of carotenoids on mitochondrial dysfunction

“…Mitophagy, which is the process of removing damaged mitochondria is impaired during pathological conditions [ 7 ]. Deregulation of MQC processes and ultimately mitochondrial dysfunction has been implicated in sarcopenia [ 16 ], glaucoma [ 17 ], lung disease [ 18 ], infection, obesity, type 2 diabetes/diabetes kidney disease [ 19 ], hepatic ischemia-reperfusion injury [ 20 ], cardiovascular disease [ 21 ], neurological diseases [ 22 ] and age-related diseases [ 9 , 23 ].…”