Oxidative stress occurs through an imbalance between the generation of reactive oxygen species (ROS) and the antioxidant defense mechanisms of cells. The eye is particularly exposed to oxidative stress because of its permanent exposure to light and due to several structures having high metabolic activities. The anterior part of the eye is highly exposed to ultraviolet (UV) radiation and possesses a complex antioxidant defense system to protect the retina from UV radiation. The posterior part of the eye exhibits high metabolic rates and oxygen consumption leading subsequently to a high production rate of ROS. Furthermore, inflammation, aging, genetic factors, and environmental pollution, are all elements promoting ROS generation and impairing antioxidant defense mechanisms and thereby representing risk factors leading to oxidative stress. An abnormal redox status was shown to be involved in the pathophysiology of various ocular diseases in the anterior and posterior segment of the eye. In this review, we aim to summarize the mechanisms of oxidative stress in ocular diseases to provide an updated understanding on the pathogenesis of common diseases affecting the ocular surface, the lens, the retina, and the optic nerve. Moreover, we discuss potential therapeutic approaches aimed at reducing oxidative stress in this context.

Age-related macular degeneration (AMD) is a common irreversible ocular disease characterized by vision impairment among older people. Many risk factors are related to AMD and interact with each other in its pathogenesis. Notably, oxidative stress and choroidal vascular dysfunction were suggested to be critically involved in AMD pathogenesis. In this review, we give an overview on the factors contributing to the pathophysiology of this multifactorial disease and discuss the role of reactive oxygen species and vascular function in more detail. Moreover, we give an overview on therapeutic strategies for patients suffering from AMD.

Many retinal diseases, such as diabetic retinopathy, glaucoma, and age-related macular (AMD) degeneration, are associated with elevated reactive oxygen species (ROS) levels. ROS are important intracellular signaling molecules that regulate numerous physiological actions, including vascular reactivity and neuron function. However, excessive ROS formation has been linked to vascular endothelial dysfunction, neuron degeneration, and inflammation in the retina. ROS can directly modify cellular molecules and impair their function. Moreover, ROS can stimulate the production of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) causing inflammation and cell death. However, there are various compounds with direct or indirect antioxidant activity that have been used to reduce ROS accumulation in animal models and humans. In this review, we report on the physiological and pathophysiological role of ROS in the retina with a special focus on the vascular system. Moreover, we present therapeutic approaches for individual retinal diseases targeting retinal signaling pathways involving ROS.

In the human cornea, regeneration of the epithelium is regulated by the stem cell reservoir of the limbus, which is the marginal region of the cornea representing the anatomical and functional border between the corneal and conjunctival epithelium. In support of this concept, extensive limbal damage, e.g., by chemical or thermal injury, inflammation, or surgery, may induce limbal stem cell deficiency (LSCD) leading to vascularization and opacification of the cornea and eventually vision loss. These acquired forms of limbal stem cell deficiency may occur uni- or bilaterally, which is important for the choice of treatment. Moreover, a variety of inherited diseases, such as congenital aniridia or dyskeratosis congenita, are characterized by LSCD typically occurring bilaterally. Several techniques of autologous and allogenic stem cell transplantation have been established. The limbus can be restored by transplantation of whole limbal grafts, small limbal biopsies or by ex vivo-expanded limbal cells. In this review, the physiology of the corneal epithelium, the pathophysiology of LSCD, and the therapeutic options will be presented.

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.

Acetylcholine regulates perfusion of numerous organs via changes in local blood flow involving muscarinic receptor-induced release of vasorelaxing agents from the endothelium. The purpose of the present study was to determine the role of M₁, M₃, and M₅muscarinic acetylcholine receptors in vasodilation of small arteries using gene-targeted mice deficient in either of the three receptor subtypes (M1R^−/−, M3R^−/−, or M5R^−/−mice, respectively). Muscarinic receptor gene expression was determined in murine cutaneous, skeletal muscle, and renal interlobar arteries using real-time PCR. Moreover, respective arteries from M1R^−/−, M3R^−/−, M5R^−/−, and wild-type mice were isolated, cannulated with micropipettes, and pressurized. Luminal diameter was measured using video microscopy. mRNA for all five muscarinic receptor subtypes was detected in all three vascular preparations from wild-type mice. However, M₃receptor mRNA was found to be most abundant. Acetylcholine produced dose-dependent dilation in all three vascular preparations from M1R^−/−, M5R^−/−, and wild-type mice. In contrast, cholinergic dilation was virtually abolished in arteries from M3R^−/−mice. Deletion of either M₁, M₃, or M₅receptor genes did not affect responses to nonmuscarinic vasodilators, such as substance P and nitroprusside. These findings provide the first direct evidence that M₃receptors mediate cholinergic vasodilation in cutaneous, skeletal muscle, and renal interlobar arteries. In contrast, neither M₁nor M₅receptors appear to be involved in cholinergic responses of the three vascular preparations tested.