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2015 ; 21
(ä): 1060-70
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Increased levels of extracellular ATP in glaucomatous retinas: Possible role of
the vesicular nucleotide transporter during the development of the pathology
#MMPMID26392744
Pérez de Lara MJ
; Guzmán-Aránguez A
; de la Villa P
; Díaz-Hernández JI
; Miras-Portugal MT
; Pintor J
Mol Vis
2015[]; 21
(ä): 1060-70
PMID26392744
show ga
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.
|Adenosine Triphosphate/*metabolism
[MESH]
|Aging/*metabolism
[MESH]
|Animals
[MESH]
|Biological Transport
[MESH]
|Disease Models, Animal
[MESH]
|Disease Progression
[MESH]
|Electroretinography
[MESH]
|Female
[MESH]
|Gene Expression
[MESH]
|Glaucoma/genetics/*metabolism/pathology
[MESH]
|Intraocular Pressure
[MESH]
|Mice
[MESH]
|Mice, Inbred C57BL
[MESH]
|Mice, Inbred DBA
[MESH]
|Nucleotide Transport Proteins/genetics/*metabolism
[MESH]