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R. Gallego-Pinazo, V. C. Zanon-Moreno, M. D. Pinazo-Duran, J. J. Garcia-Medina, F. J. Cruz-Espinosa, I. Vinuesa Silva; Antioxidant Activity, Nitric Oxide and P53 GeneIn Primary Open Angle Glaucoma. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5106.
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Among the key mediators for glaucoma damage oxidants and nitric oxide have been largely implicated. Antioxidants (AOX) have shown a cooperative protective effect against apoptosis. Others, as the p53 gene plays pivotal regulatory activities in order to trigger biological responses, the most notable cell-cycle arrest and cell death by apoptosis in response to several factors, such as oxidative stress. Our main goal is to analyze the different ways these molecules may act, and the connecting mechanisms between them in the pathogenic mechanisms of primary open angle glaucoma (POAG).
Aqueous humor was obtained from patients distributed into two groups: 1) POAG patients (n=208) and 2) comparative subjects operated of cataracts (CG; n=284). Samples were extracted at onset of surgery, frozen (-85ºC) and stored for biochemical processing. Assays for determining AOX activity [total reactive AOX (TRA); superoxide dismutase (SOD)] and NO levels (by means of nitrate reductase) were carried out. The retina-choroid and optic nerve were obtained from C57BL/6 transgenic mice over-expressing p53 gene (Sp53) and normal wild type (Cwt) mice. Samples were frozen (-85ºC) and stored until preparing homogenates in order to determine TRA. All data were statistically analysed.
Significantly lower values of TRA (p<0,001), but higher SOD (p<0,05) levels were found in the POAG patients than in the CG. NO levels were significantly higher in the POAG group respect to the cataract patients (p<0,05). In addition, significantly increased AOX activity was found in the eye tissues from the transgenic Sp53 mice (p<0,001) respect to the Cwt mice.
The neurotoxic potential to induce glaucomatous ganglion cell and optic fibre degeneration/death is supported by the decreased AOX activity and the increased NO availability displayed by the glaucoma patients. The animal model showed that the presence of an extra copy of p53 gene correlated with an intrinsic switch clock for oxidative stress, by enhancing the AOX activity in the ocular cells. Further research on these latter molecules may facilitate development of new management strategies for avoiding glaucomatous optic atrophy and blindness, including the genetic control of oxidative stress and apoptosis involving p53.
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