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Title: Elevated Pressure Changes the Purinergic System of Microglial Cells
Authors: Rodrigues-Neves, Ana C. 
Aires, Inês D. 
Vindeirinho, Joana R. 
Boia, Raquel 
Madeira, Maria H. 
Gonçalves, Francisco Q. 
Cunha, Rodrigo A. 
Santos, Paulo 
Ambrósio, Francisco 
Santiago, Ana R. 
Keywords: purinergic system; ATP; adenosine; microglia; elevated pressure; glaucoma
Issue Date: 2018
Publisher: Frontiers Media S.A.
Project: Project PTDC/BIMMEC/ 0913/2012 
PEst-C/SAU/UI3282/ 2013 
FEDER-COMPETE (POCI- 01-0145-FEDER-007440) 
Centro 2020 Regional Operational Programme (CENTRO-01-0145-FEDER-000008: BrainHealth 2020) 
Serial title, monograph or event: Frontiers in Pharmacology
Volume: 9
Issue: JAN
Abstract: Glaucoma is the second cause of blindness worldwide and is characterized by the degeneration of retinal ganglion cells (RGCs) and optic nerve atrophy. Increased microglia reactivity is an early event in glaucoma that may precede the loss of RGCs, suggesting that microglia and neuroinflammation are involved in the pathophysiology of this disease. Although global changes of the purinergic system have been reported in experimental and human glaucoma, it is not known if this is due to alterations of the purinergic system of microglial cells, the resident immune cells of the central nervous system. We now studied if elevated hydrostatic pressure (EHP), mimicking ocular hypertension, changed the extracellular levels of ATP and adenosine and the expression, density and activity of enzymes, transporters and receptors defining the purinergic system. The exposure of the murine microglial BV-2 cell line to EHP increased the extracellular levels of ATP and adenosine, increased the density of ecto-nucleoside triphosphate diphosphohydrolase 1 (E-NTPDase1, CD39) and decreased the density of the equilibrative nucleotide transporter 2 as well as the activity of adenosine deaminase. The expression of adenosine A1 receptor also decreased, but the adenosine A3 receptor was not affected. Notably, ATP and adenosine selectively control migration rather than phagocytosis, both bolstered by EHP. The results show that the purinergic system is altered in microglia in conditions of elevated pressure. Understanding the impact of elevated pressure on the purinergic system will help to unravel the mechanisms underlying inflammation and neurodegeneration associated with glaucoma.
ISSN: 1663-9812
DOI: 10.3389/fphar.2018.00016
Rights: openAccess
Appears in Collections:I&D IBILI - Artigos em Revistas Internacionais
FMUC Medicina - Artigos em Revistas Internacionais
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I&D CNC - Artigos em Revistas Internacionais

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