[Oxidative stress and pseudoexfoliation glaucoma]

Abstract

Pseudoexfoliation (PEX) glaucoma is the most common identifiable cause of open-angle glaucoma worldwide, comprising the majority of glaucoma in some countries. The underlying disorder, PEX syndrome, is a generalised, genetically determined, elastotic process of the extracellular matrix characterised by the excessive production and progressive accumulation of a fibrillar material in various tissues including the outflow pathways. Increasing evidence suggests that the oxidative-antioxidative balance is disturbed in patients with PEX syndrome/glaucoma, both in the anterior segment and throughout the body, and that the resulting oxidative stress constitutes a major mechanism involved in the pathophysiology of this fibrotic process. Significantly reduced levels of antioxidants, such as ascorbic acid, glutathione, trace elements, antioxidative enzymes, and total antioxidative capacity in aqueous humor and serum suggest a faulty antioxidative defense system in PEX patients. The down-regulation of antioxidative enzymes in anterior segment tissues also indicates an inadequate cytoprotection against oxidative stress. Concomitantly, levels of oxidants such as hydrogen peroxide or nitric oxide, and oxidative stress markers, including lipid peroxidation products, degradation products of oxidated and methylated proteins, advanced glycation end products, and homocysteine are significantly increased in aqueous humor, tissues, and serum. The available data suggest that chronic oxidative stress in combination with weakened cytoprotective and repair strategies affects the abnormal matrix metabolism by induction of a persistent pro-inflammatory state and activation of the profibrotic growth factor TGF-beta1. Oxidative stress, therefore, appears to represent a modifiable risk factor in the management of patients with PEX syndrome/glaucoma.