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Jesus J Pintor, Maria J Perez de Lara; Changes in the purinergic system in the retina of a glaucomatous model. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2438.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the changes in the purinergic system in the retina by studying the changes in P2X7 receptors, VNUT transporters and ATP levels in normal and in a murine model of glaucoma.
Retinas were obtained from the glaucomatous DBA/2J mice at 3, 9, 15 and 22 months together with C57BL/6J mice used as age-matched controls. In order to investigate P2X7 and VNUT expression, sections of mouse retinas were evaluated by western blots and immunohistochemistry studies using developed antibodies against P2X7 and VNUT. For the study of retinal nucleotide release, retinas were dissected and prepared as flattened whole-mounts and were stimulated with Ringer buffer with or without 59 mM KCl. ERG recordings were performed on C57BL/6J and DBA/2J mice to analyse the changes in the electrophysiological response. IOP was also measured by means a Tono Lab tonometer, at the indicated animal ages, both in normal and glaucomatous mice.
Glaucomatous mice exhibited changes in the retinal ATP net release as long as the pathology progressed, varying from 0.32 ± 0.04 pmol/retina (3 months) to 1.10 ± 0.06 pmol/retina (15 months) (3-fold increase). Concomitantly, VNUT expression was significantly increased along glaucoma progression in the DBA/2J mice (58%) when followed either by immunohistochemical and western-blot techniques. Our results may indicate a possible correlation of retinal dysfunction with the increased levels of extracellular ATP and nucleotide transporter probably by the nucleotide interacting with P2X7R present in the retinas of the animal models. This is in part due to the increase in the expression of P2X7 receptors which changed 36 % during the time from 3 months to 15 months in the DBA glaucomatous model.
Changes in ATP, VNUT and P2X7 receptor expression may be, at least in part, responsible for the changes in the retina observed in the DBA/2J glaucomatous model. The elevated levels of ATP can activate P2X7 receptors, that may produce retinal cell death since this receptor has been described as a pro-apoptotic receptor.
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