Mitochondrial Dysfunction and Oxidative Stress in Eye Diseases: Mechanistic Insights and Therapies

Mitochondrial dysfunction and oxidative stress are being increasingly identified as a core pathogenesis mechanism of a number of ocular diseases. The eye is a highly metabolically active organ and thus depends mostly on the mitochondria’s oxidative phosphorylation to supply its energy needs. Mitochondrial dysfunction causes an over-production of reactive oxygen species, which causes oxidative stress to cellular components such as lipids, proteins, and deoxyribonucleic acid. This disproportion leads to defective cellular homeostasis, inflammation, and apoptosis, which eventually leads to degenerative changes in ocular tissues. Photoreceptors, retinal ganglion cells, retinal pigment epithelium, and corneal endothelial cells are especially susceptible to environmental stresses because they are highly metabolic and subjected to continuous exposure to environmental stressors, including light and oxygen. Mitochondrial dysfunction has been attributed to significant eye diseases such as age-related macular degeneration, glaucoma, diabetic retinopathy, and inherited optic neuropathies. These diseases have a pathophysiology in common characterized by bioenergetic dysfunction, oxidative damage, and progressive cellular death. Recent research has been directed at the treatment approaches that involve mitochondrial pathways, such as mitochondria-specific antioxidants, gene therapy, and stem cell-based approaches. Although preclinical research indicates positive outcomes, clinical translation has been low because of hurdles like the barriers to drug delivery, inconsistent reactions in patients, and the absence of standard biomarkers. This review puts into perspective the mechanistic interaction between mitochondrial dysfunction and oxidative stress in ocular diseases and the significance of combined, focused therapeutic strategies. Further insight into such pathways can help to work out the efficient interventions that would help to save vision and delay the development of the disease.