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Potential role of P2X7 receptor in neurodegenerative processes in a murine model of glaucoma

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Pérez de Lara, María Jesús and Avilés Trigueros, Marcelino and Guzmán Aránguez, Ana Isabel and Valiente Soriano, Francisco Javier and Villa Polo, Pedro de la and Vidal Sanz, Manuel and Pintor, Jesús (2019) Potential role of P2X7 receptor in neurodegenerative processes in a murine model of glaucoma. Brain Research Bulletin, 150 . pp. 61-74. ISSN 0361-9230

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Official URL: https://doi.org/10.1016/j.brainresbull.2019.05.006




Abstract

Glaucoma is a common cause of visual impairment and blindness, characterized by retinal ganglion cell (RGC) death. The mechanisms that trigger the development of glaucoma remain unknown and have gained significant relevance in the study of this neurodegenerative disease. P2X7 purinergic receptors (P2X7R) could be involved in the regulation of the synaptic transmission and neuronal death in the retina through different pathways. The aim of this study was to characterize the molecular signals underlying glaucomatous retinal injury.
The time-course of functional, morphological, and molecular changes in the glaucomatous retina of the DBA/2J mice were investigated. The expression and localization of P2X7R was analysed in relation with retinal markers. Caspase-3, JNK, and p38 were evaluated in control and glaucomatous mice by immunohistochemical and western-blot analysis. Furthermore, electroretinogram recordings (ERG) were performed to assess inner retina dysfunction.
Glaucomatous mice exhibited changes in P2X7R expression as long as the pathology progressed. There was P2X7R overexpression in RGCs, the primary injured neurons, which correlated with the loss of function through ERG measurements. All analyzed MAPK and caspase-3 proteins were upregulated in the DBA/2J retinas suggesting a pro-apoptotic cell death.
The increase in P2X7Rs presence may contribute, together with other factors, to the changes in retinal functionality and the concomitant death of RGCs. These findings provide evidence of possible intracellular pathways responsible for apoptosis regulation during glaucomatous degeneration.


Item Type:Article
Additional Information:

Received 28 August 2018, Revised 23 April 2019, Accepted 10 May 2019, Available online 16 May 2019.
This article is dedicated to Prof. Jesús Pintor, who died at the time this manuscript was under revision.

Uncontrolled Keywords:Glaucoma; Retinal ganglion cells (RGC); Neuronal degeneration; Apoptosis; Electroretinogram (ERG); P2X7; MAPK
Subjects:Medical sciences > Medicine > Neurosciences
Medical sciences > Medicine > Ophtalmology
Medical sciences > Optics > Eyes anatomy
Medical sciences > Optics > Imaging systems
ID Code:55836
Deposited On:19 Jun 2019 10:54
Last Modified:19 Jun 2019 11:15

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