Imbalanced mitochondrial homeostasis in ocular diseases: unique pathogenesis and targeted therapy

Abstract

Mitochondria play a crucial role in energy production and are intimately associated with ocular function. Mitochondrial dysfunction can trigger oxidative stress and inflammation, adversely affecting key ocular structures such as the lacrimal gland, lens, retina, and trabecular meshwork. This dysfunction may compromise the barrier properties of the trabecular meshwork, impeding aqueous humour outflow, elevating intraocular pressure, and resulting in optic nerve damage and primary open-angle glaucoma. Additionally, impaired mitochondrial homeostasis can contribute to dry eye, cataracts, and age-related macular degeneration (AMD) by disrupting the function of the lacrimal gland, lens, and macula. Imbalanced mitochondrial homeostasis primarily involves four pathological features: disruption of mitochondrial quality control, mitochondrial damage (inducing inflammation), excessive production of mitochondrial reactive oxygen species (ROS) (initiating oxidative stress), and disturbances in mitochondrial calcium (Ca²⁺) homeostasis. Oxidative stress and inflammation are central mechanisms of cellular injury. Pharmacological strategies aimed at reducing excessive ROS, restoring redox balance, and mitigating oxidative and inflammatory damage show therapeutic promise. Moreover, enhancing mitochondrial function through pharmacological agents, replacing damaged mitochondria, and promoting mitochondrial rejuvenation represent emerging treatment avenues. This review explores the relationship between mitochondrial dysfunction and ocular diseases such as dry eye, glaucoma, cataracts, and AMD, with a focus on associated mechanisms and potential therapeutic interventions.