Eicosanoids and Oxidative Stress in Diabetic Retinopathy

Abstract

Oxidative stress is an important factor to cause the pathogenesis of diabetic retinopathy (DR) because the retina has high vascularization and long-time light exposition. Cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP) enzymes can convert arachidonic acid (AA) into eicosanoids, which are important lipid mediators to regulate DR development. COX-derived metabolites appear to be significant factors causative to oxidative stress and retinal microvascular dysfunction. Several elegant studies have unraveled the importance of LOX-derived eicosanoids, including LTs and HETEs, to oxidative stress and retinal microvascular dysfunction. The role of CYP eicosanoids in DR is yet to be explored. There is clear evidence that CYP-derived epoxyeicosatrienoic acids (EETs) have detrimental effects on the retina. Our recent study showed that the renin-angiotensin system (RAS) activation augments retinal soluble epoxide hydrolase (sEH), a crucial enzyme degrading EETs. Our findings suggest that EETs blockade can enhance the ability of RAS blockade to prevent or mitigate microvascular damage in DR. This review will focus on the critical information related the function of these eicosanoids in the retina, the interaction between eicosanoids and reactive oxygen species (ROS), and the involvement of eicosanoids in DR. We also identify potential targets for the treatment of DR.

Antioxidative Effects of Ascorbic Acid and Astaxanthin on ARPE-19 Cells in an Oxidative Stress Model

“…Although the role of retinal endothelial cells comprising inner blood-retinal barriers (BRB) is important in DR development, the role of RPE cells comprising outer BRB is also crucial. The flow of nutrients materials, metabolites, ions, proteins, and water flux to and from the retina is regulated by these two BRBs and disruption of inner and outer BRB causes retinal hyperpermeability and development of diabetic macular edema, which is a leading cause of vision loss in DR [ 55 ]. Therefore, current study using ARPE-19 cells is thought be closely related to BRB breakdown and the pathogenesis of DR. Oxidative damage to cells is commonly modeled using treatment with H 2 O 2 for a long time [ 56 , 57 ], however, very little is known about the role of UV irradiation on ARPE-19 cells and especially on the development of DR. A recent population-based study investigated the association between daily sunlight exposure duration and DR [ 58 ].…”

Protective Effects and Molecular Signaling of n-3 Fatty Acids on Oxidative Stress and Inflammation in Retinal Diseases

“…Eicosanoids generation by COX, lipoxygenase, and cytochrome P450 enzymes from arachidonic acid (AA) indicate that the eicosanoids can induce oxidative stress, inflammation, and vascular function as lipid mediators [ 30 ]. Although AA is also an essential component of cell membranes and plays an integral role in growth during fetal development [ 31 ], n-6 fatty acids, including AA, have been strongly linked to inflammation [ 32 ].…”

Development of Tandem Mass Tag Labeling Method for Lipid Molecules Containing Carboxy and Phosphate Groups, and Their Stability in Human Serum

“…For eicosanoids, 12-HETE (hydroxyeicosatetraenoic acid) tended to increase ( Figure 7 A) after incubation, for example, whereas 20-/18-/15-HETE tended to decrease in serum levels ( Figure 7 B). Since 12-HETE and 15-HETE are downstream of lipoxygenase enzymes and 18-HETE and 20-HETE are produced by a cytochrome P450 enzyme, it is not surprising that the activity of these enzymes is influenced by diseases [ 33 ]. In disease samples, thromboxane B 2 (TXB 2 ) tended to decrease in serum after incubation, especially for patients with schizophrenia ( Figure 7 C).…”