Increased levels of extracellular ATP in glaucomatous retinas: Possible role of the vesicular nucleotide transporter during the development of the pathology



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Pérez de Lara, María Jesús and Guzmán Aránguez, Ana Isabel and Villa, Pedro, de la and Díaz Hernández, Juan Ignacio and Miras Portugal, María Teresa and Pintor, Jesús (2015) Increased levels of extracellular ATP in glaucomatous retinas: Possible role of the vesicular nucleotide transporter during the development of the pathology. Molecular Vision, 21 . p. 10. ISSN 1090-0535

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Purpose: To study retinal extracellular ATP levels and to assess the changes in the vesicular nucleotide transporter (VNUT) expression in a murine model of glaucoma during the development of the disease.
Methods: Retinas were obtained from glaucomatous DBA/2J mice at 3, 9, 15, and 22 months together with C57BL/6J mice used as age-matched controls. To study retinal nucleotide release, the retinas were dissected and prepared as flattened whole mounts and stimulated in Ringer buffer with or without 59 mM KCl. To investigate VNUT expression, sections of the mouse retinas were evaluated with immunohistochemistry and western blot analysis using newly developed antibodies against VNUT. All images were examined and photographed under confocal microscopy. Electroretinogram (ERG) recordings were performed on the C57BL/6J and DBA/2J mice to analyze the changes in the electrophysiological response; a decrease in the scotopic threshold response was observed in the 15-month-old DBA/2J mice.
Results: In the 15-month-old control and glaucomatous mice, electrophysiological changes of 42% were observed. In addition, 50% increases in the intraocular pressure (IOP) were observed when the pathology was fully established. The responses in the retinal ATP net release as the pathology progressed varied from 0.32±0.04 pmol/retina (3 months) to 1.10±0.06 pmol/retina (15 months; threefold increase). Concomitantly, VNUT expression was significantly increased during glaucoma progression in the DBA/2J mice (58%) according to the immunohistochemical and western blot analysis.
Conclusions: These results may indicate a possible correlation between retinal dysfunction and increased levels of extracellular ATP and nucleotide transporter. These data support an excitotoxicity role for ATP via P2X7R in glaucoma. This modified cellular environment could contribute to explaining the functional and biochemical alterations observed during the development of the pathology.

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En O.A. en la web del editor.
Received 05 June 2015 | Accepted 31 August 2015 | Published 02 September 2015

Uncontrolled Keywords:Disease models, animal ; Electroretinography ; Glaucoma ; Intraocular pressure ; Nucleotide trasport proteins ; Adenosine triphosphate
Subjects:Medical sciences > Medicine > Biochemistry
Medical sciences > Medicine > Ophtalmology
ID Code:41714
Deposited On:10 Mar 2017 11:39
Last Modified:13 Mar 2017 16:18

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