Oxidative Stress: A Suitable Therapeutic Target for Optic Nerve Diseases?

Abstract

Optic nerve disorders encompass a wide spectrum of conditions characterized by the loss of retinal ganglion cells (RGCs) and subsequent degeneration of the optic nerve. The etiology of these disorders can vary significantly, but emerging research highlights the crucial role of oxidative stress, an imbalance in the redox status characterized by an excess of reactive oxygen species (ROS), in driving cell death through apoptosis, autophagy, and inflammation. This review provides an overview of ROS-related processes underlying four extensively studied optic nerve diseases: glaucoma, Leber’s hereditary optic neuropathy (LHON), anterior ischemic optic neuropathy (AION), and optic neuritis (ON). Furthermore, we present preclinical findings on antioxidants, with the objective of evaluating the potential therapeutic benefits of targeting oxidative stress in the treatment of optic neuropathies.

Pathways controlling neurotoxicity and proteostasis in mitochondrial complex I deficiency

“…The retina is highly metabolically active [ 46 ]. Proper electron transport chain function is not only critical to meet the substantial energy demand of the retina, but also to maintain redox balance and cytosolic pH, alterations of which can both lead to overproduction of reactive oxygen species [ 47 ]. Indeed, oxidative stress is a consistent feature of cellular and animal models of complex I deficiency based on Leber’s hereditary optic neuropathy mitochondrial mutations, in some cases without clear reduction in ATP levels [ 48 ].…”

Aging in Ocular Blood Vessels: Molecular Insights and the Role of Oxidative Stress

“…Oxidative stress impacts vascular function through protein oxidation, redox-sensitive transcription factor induction, and, notably, the deactivation of endothelium-derived nitric oxide (NO) [145]. Factors influencing NO bioavailability encompass ROS, endothelial NO synthase (eNOS) activation status, and changes in substrate (L-arginine) and cofactor (tetrahydrobiopterin, BH 4 ) availability [27].…”

Retinopathy of Prematurity—Targeting Hypoxic and Redox Signaling Pathways

“…Nitro-oxidative stress, characterized by an imbalance between the abundant generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and antioxidative defense mechanisms, leads to excess ROS and RNS. This imbalance triggers dramatic structural molecular changes and the activation of inflammatory and cell death pathways, a condition detectable in various eye diseases [88,89]. It is noteworthy that infants possess reduced antioxidant defenses [90].…”