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Editors Selection IGR 14-3
Basic research: Oxidative stress
Comment by Ernst Tamm on:
11958 Oxidative DNA damage in the human trabecular meshwork: clinical correlation in patients with primary open-angle glaucoma, Sacca SC; Pascotto A; Camicione P et al., Archives of Ophthalmology, 2005; 123: 458-463
It has been a long standing hypothesis that oxidative stress causes or contributes to damage of trabecular meshwork (TM) cells, which may be a key factor for the generation of glaucomatous damage. In support of this, Wang and coworkers (Nat. Med. 2001) showed a couple of years ago that the endothelial leukocyte adhesion molecule-1/interleukin-1/nuclear factor kB pathway is activated in TM cells that were collected from patients with primary open angle glaucoma (POAG). In a recent study, Saccà et al. (44) turned their attention to the question, if the DNA of TM cells from patients with POAG shows signs of oxidative damage. Oxidative damage of DNA may lead to the modification of nucleotides, the formation of molecular cross links, the formation of DNA mutations and finally to cell death. Saccà et al. examined the levels of 8-hydroxy-2'-deoxyguanosine (8-OH-dG), a molecular marker for oxidative damage of DNA. Levels of 8-OH-dG were statistically higher (five-fold) in TM samples from POAG patients that were collected during filtration surgery than in normal controls. A significant correlation was found among TM DNA oxidative damage, visual field damage and intraocular pressure. These are certainly interesting data that add to the concept of oxidative stress causing or contributing to TM damage and POAG. Still, some additional factors need to be considered. One of these factors is medical treatment of POAG. Treatment of POAG patients with compounds that decrease aqueous humor secretion may cause a relative increase in oxidative species such as hydrogen peroxide in the aqueous humor. Thus the oxidative burden of the TM may be increased beyond a level that is damaging to TM cells. In this case, oxidative molecular damage to TM cells would be rather a symptom than the cause of glaucoma.
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