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Editors Selection IGR 17-1

Basic Science: Aquous humor proteomics in glaucoma

Comment by Franz Grus on:

51266 Aqueous humor oxidative stress proteomic levels in primary open angle glaucoma, Bagnis A; Izzotti A; Centofanti M et al., Experimental Eye Research, 2012; 103: 55-62

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The influence of aqueous humor production and outflow on intraocular pressure (IOP), which is still an important risk factor for primary open-angle glaucoma (POAG), is well known. Recently, oxidative stress through reactive oxygen species (ROS) targeting the trabecular meshwork TM is discussed as possible cause of cell death and increased IOP in glaucoma. Aqueous humor with its anti-oxidative properties could represent a barrier against this kind of damage. The current study of Bagnis et al. therefore aimed to answer the question if this anti-oxidative capacity is detectably decreased in POAG. The casecontrol study included ten patients with POAG and ten age- and gender-matched cataract controls. Aqueous humor was analyzed via antibody microarray to test the expression of proteins in a dye-swapping procedure. The focus of this work was the investigation of proteomic levels of enzymes showing oxidative production/detoxification activities like glutamine synthase (GS), nitric oxide synthase (NOS), superoxide dismutase (SOD) and glutathione transferase (GST). The authors could show significantly higher levels of pro-oxidant enzymes NOS and GS as well as lower levels of anti-oxidant enzymes SOD and GST in glaucoma samples, in the latter case validated with enzyme activity measurement in the native samples. The authors propose that a higher level of NOS and reduced level of SOD and GST affect the cellularity of the TM by accumulation of reactive oxygen and nitrogen species, followed by an increase of cell lipid peroxidation. Altered TM functioning could therefore lead to increased IOP and higher levels of glutamate which could be a reason for increased expression of GS in POAG patients. The work presented was carefully performed; patients as well as methodical approach are both well described. While a potential influence of glaucoma medication on enzyme activities could not be fully excluded, these findings may provide further evidence for potential influence of oxidative stress in POAG pathophysiology. However, it needs to be considered that the number of patients was extremely small and therefore the value of the information limited and can only be seen as first pilot study.

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