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.

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.

Diabetic retinopathy (DR) represents a severe complication of diabetes mellitus, characterized by irreversible visual impairment resulting from microvascular abnormalities. Since the global prevalence of diabetes continues to escalate, DR has emerged as a prominent area of research interest. The development and progression of DR encompass a complex interplay of pathological and physiological mechanisms, such as high glucose-induced oxidative stress, immune responses, vascular endothelial dysfunction, as well as damage to retinal neurons. Recent years have unveiled the involvement of genomic and epigenetic factors in the formation of DR mechanisms. At present, extensive research explores the potential of biomarkers such as cytokines, molecular and cell therapies, antioxidant interventions, and gene therapy for DR treatment. Notably, certain drugs, such as anti-VEGF agents, antioxidants, inhibitors of inflammatory responses, and protein kinase C (PKC)-β inhibitors, have demonstrated promising outcomes in clinical trials. Within this context, this review article aims to introduce the recent molecular research on DR and highlight the current progress in the field, with a particular focus on the emerging and experimental treatment strategies targeting the immune and redox signaling pathways.

Disturbances of retinal perfusion are involved in the onset and maintenance of several ocular diseases, including diabetic retinopathy, glaucoma, and retinal vascular occlusion. Hence, knowledge on ocular vascular anatomy and function is highly relevant for basic research studies and for clinical judgment and treatment. The retinal vasculature is composed of the superficial, intermediate, and deep vascular layer. Detection of changes in blood flow and vascular diameter especially in smaller vessels is essential to understand and to analyze vascular diseases. Several methods to evaluate blood flow regulation in the retina have been described so far, but no gold standard has been established. For highly reliable assessment of retinal blood flow, exact determination of vessel diameter is necessary. Several measurement methods have already been reported in humans. But for further analysis of retinal vascular diseases, studies in laboratory animals, including genetically modified mice, are important. As for mice, the small vessel size is challenging requiring devices with high optic resolution. In this review, we recapitulate different methods for retinal blood flow and vessel diameter measurement. Moreover, studies in humans and in experimental animals are described.

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.

Diabetes mellitus may cause severe damage to retinal blood vessels. The central aim of this study was to test the hypothesis that sulodexide, a mixture of glycosaminoglycans, has a protective effect against hyperglycemia-induced endothelial dysfunction in the retina. Functional studies were performed in isolated porcine retinal arterioles. Vessels were cannulated and incubated with highly concentrated glucose solution (HG, 25 mM D-glucose) +/− sulodexide (50/5/0.5 μg/mL) or normally concentrated glucose solution (NG, 5.5 mM D-glucose) +/− sulodexide for two hours. Endothelium-dependent and endothelium-independent vasodilatation were measured by videomicroscopy. Reactive oxygen species (ROS) were quantified by dihydroethidium (DHE) fluorescence. Using high-pressure liquid chromatography (HPLC), the intrinsic antioxidant properties of sulodexide were investigated. Quantitative PCR was used to determine mRNA expression of regulatory, inflammatory, and redox genes in retinal arterioles, some of which were subsequently quantified at the protein level by immunofluorescence microscopy. Incubation of retinal arterioles with HG caused significant impairment of endothelium-dependent vasodilation, whereas endothelium-independent responses were not affected. In the HG group, ROS formation was markedly increased in the vascular wall. Strikingly, sulodexide had a protective effect against hyperglycemia-induced ROS formation in the vascular wall and had a concentration-dependent protective effect against endothelial dysfunction. Although sulodexide itself had only negligible antioxidant properties, it prevented hyperglycemia-induced overexpression of the pro-oxidant redox enzymes, NOX4 and NOX5. The data of the present study provide evidence that sulodexide has a protective effect against hyperglycemia-induced oxidative stress and endothelial dysfunction in porcine retinal arterioles, possibly by modulation of redox enzyme expression.