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Jesus Pintor, Pedro de la Villa, Maria Jesus Perez de Lara; CHANGES IN RETINAL P2X7 RECEPTORS IN A MURINE MODEL OF GLAUCOMA. Invest. Ophthalmol. Vis. Sci. 2013;54(15):772. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the changes in the P2X7 receptor in a murine model of glaucoma during the development of the disease.
DBA/2J glaucomatous mice together with C57BL/6J control mice were used along the whole experimentation. Animals were studied from 3 till 15 months of age. For the study of retinal nucleotide release retinas were dissected and prepared as flattened whole-mounts and stimulated in Ringer solution buffer with or without 59 mM KCl. Immunohistochemical, western-blot and PCR analyses were performed with antibodies against the nucleotide vesicular transporter VNUT and the P2X7 nucleotide receptor. ERG recordings were performed on the right eyes of C57BL/6J and DBA/2J mice at different ages (3-15 months) to analyze the changes in the electrophysiological response. Scotopic threshold response determines the onset of functional changes exhibited in the inner retina of the DBA/2J mice.
Glaucomatous mice exhibited changes in retinal ATP release as long as the pathology progressed. Changes occurred when compared to those animals without the pathology which basal retinal ATP level was 6.56 ±1.81 pmol/retina while the stimulated with KCl was 9.64 ± 1.45 pmol/retina. ATP came mainly from synaptic vesicles since the nucleotide transporter marker VNUT label mainly the inner plexiform layer. Concerning the distribution of P2X7 receptor it was possible to measure a clear increase in the presence of this nucleotide receptor with glaucoma progression in the DBA/2J mice. There was 36 % of increase in the presence of this receptor measured both by immunohistochemical and western-blot techniques. It was also possible to see that at 15 months of age the glaucomatous mice presented 78 % more expression of retinal P2X7 receptors than in control (C57BL/6J) mice. ERG recordings in 15 months glaucomatous mice showed an important/ reduction in the pSTR response correlated with ganglion cell loss.
In the development of the glaucomatous pathology in the DBA/2J mice, the increase in the presence of P2X7 receptors may contribute, together with other factors, to the changes in the functionality of the retina and the concomitant death of retinal ganglion cells.
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