Key Role of 12-Lipoxygenase and Its Metabolite 12-Hydroxyeicosatetraenoic Acid (12-HETE) in Diabetic Retinopathy

Purpose Abnormal lipid metabolism has been proved to be implicated in the complex pathogenesis of diabetic retinopathy (DR). 12-lipoxygenase (12-LOX) is a member of lipoxygenase family responsible for the oxygenation of cellular polyunsaturated fatty acids to produce lipid mediators which modulate cell inflammation. This review explores the role of 12-lipoxygenase and its products in the pathogenesis of DR. Methods A comprehensive medical literature search was conducted on PubMed till September 2021. Results Emerging evidence has demonstrated that 12-LOX and its main product 12- hydroxyeicosatetraenoic acid (12-HETE) activate retinal cells, especially retinal vascular endothelial cells, through the activation of NADPH oxidase and the subsequent generation of reactive oxygen species (ROS), mediating multiple pathological changes during DR. Genetic deletion or pharmacological inhibition models of 12-LOX in mice show protection from DR. Conclusion 12-LOX and its product 12-HETE take important part in DR pathogenesis and show their potential as future therapeutic targets for DR. Further studies are needed on the specific mechanism including 12-LOX pathway related molecules, 12-HETE receptors and downstream signaling pathways.