Review of the Role of Oxidative Stress in Ocular Surface Disease and Use of MDA and 4-HNE in Tears as Potential Markers

This article addresses the possible use of malondialdehyde (MDA) and 4-hydroxy-2-nonenal (4-HNE) as biomarkers in the tears for diagnosis, determining disease severity, and monitoring the effect of treatment for dry eye disease (DED), a disease which is highly prevalent and heterogeneous with an incompletely understood pathogenesis and limited therapeutic options. The current diagnosis and classification of severity of DED is a mostly subjective process with no consistent objective markers of disease, so the identification of novel biomarkers could improve patient care as well as lead to a better understanding of the disease pathogenesis and discovery of new treatments. This review is the first to compare the results of studies of markers of oxidative stress MDA and 4-HNE in DED and other ocular diseases to more comprehensively explore the potential for the use of MDA and 4-HNE as biomarkers for DED. The role of oxidative stress in DED is reviewed and then the evidence of their association with DED and other ocular diseases. Overall, previous studies indicate a promising potential for the use of tear MDA and 4-HNE as biomarkers for DED that should be explored with further research. Abbreviations: MDA: Malondialdehyde, HNE: Hydroxy-2-Nonenal, DED: Dry Eye Disease, ROS: Reactive Oxygen Species, PUFA: Polyunsaturated Fatty Acids, L: Lipid Radical, LOO: Lipid Peroxy Radical, LOOH: Lipid Peroxidation Are Lipid Hydroperoxides, AA: Arachidonic Acid, TBA: Thiobarbituric Acid, HPLC: High-Performance Liquid Chromatography, HCEC: Human Corneal Epithelial Cells, HEL: Hexanoyl-Lysine, GCD: Granular Corneal Dystrophy, CSCR: Central Serous Chorioretinopathy, SS: Sjögren Syndrome, PS: Pterostilbene, PACG: Primary Angle-Closure Glaucoma, AKC: Atopic Keratoconjunctivitis, VF: Visual Field, KC: Keratoconus, wAMD: Wet Age Related Macular Degeneration, dAMD: Dry Age Related Macular Degeneration, S: Supplementation