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ROLE OF P2X7 RECEPTOR IN THE SURVIVAL OF AXOTOMIZED RETINAL GANGLION CELLS.
Autores:
CARIDAD GALINDO ROMERO
,
FRANCISCO MANUEL NADAL NICOLAS
,
FRANCISCO JAVIER VALIENTE SORIANO
, MANUEL SALINAS NAVARRO, MARÍA BARBERÁ CREMADES,
CARLOS DE TORRE MINGUELA
,
PABLO PELEGRIN VIVANCOS
,
MARTA AGUDO BARRIUSO
,
Grupos de investigación:
[GI/IMIB/C003/2011] Cirugía digestiva, endocrina y trasplante de órganos abdominales
[GI/IMIB/C004/2011] Oftalmología Experimental
Comunicación:
Antecedentes:
After an axonal injury, neurons that are affected degenerate and microglial cells are activated, in order to clear the death neurons by phagocytosis and also to release proinflammatory factors. Because neuronal degeneration is always conditioned by the inflammation, here we studied the P2X7 receptor as an important component for the neuronal death in a model of optic nerve axotomy.
Métodos:
Using knock-out P2X7 mice, optic nerve axotomy was carried out in the left eye and right eye was used to analyze the contralateral effect. Retinal ganglion cell (RGC) survival was analyzed at different time-points after the axotomy, using a neuronal tracer (OHSt) and Brn3a immunostaining. Retinas were dissected as flat-mounts and the total number of surviving RGCs was automatically quantified and isodensity maps were generated to study their topographical distribution. In the same retinas, phagocytic microglial cells (PMCs), transcellular labeled with OHSt, were also analyzed.
Resultados:
We have found that in P2X7 receptor deficient mice there is a delayed loss of retinal ganglion cells and a decrease of phagocytic microglia at early times points after axotomy. In contralateral to the axotomy retinas, P2X7 receptor controlled the numbers of phagocytic microglia, suggesting that extracellular ATP could act as a danger signal activating the P2X7 receptor in mediating the loss of neurons in contralateral retinas.
Conclusiones:
P2X7 receptor signaling is involved in neuronal cell death after axonal injury, being P2X7 receptor antagonism a potential therapy to delay neuronal loss after traumatic injury. Unpublished results. Colaboration between Grupo Oftalmología experimental and Grupo Inflamación Molecular
Instituto de Investigación Sanitaria Acreditado
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