UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

P2X7 Receptor Modulation of Visual Responses in the Retina

Chavda, S; (2015) P2X7 Receptor Modulation of Visual Responses in the Retina. Doctoral thesis , UCL (University College London). Green open access

[img] PDF
Seetal Chavda_PhD Thesis_2015.pdf
Available under License : See the attached licence file.

Download (9MB)

Abstract

Adenosine 5’ triphosphate (ATP)-gated P2X7 receptors (P2X7Rs) are known to act as conduits for photoreceptor and retinal ganglion cell (RGC) damage, consequences of various neurodegenerative conditions within the visual pathway. Growing evidence supports the notion that P2X7Rs and associated inflammatory mediators may coordinate microglia, the resident immune cells of the central nervous system (CNS), to play a genuine role in modulating neurotransmission. This study aimed to characterise the role of P2X7Rs in modulating outer and inner retinal function within the rod-mediated pathway, and in the putative microglial-mediated modulation of signal transmission in the retina. Excitatory components of outer and inner retinal function were assessed by recording light-evoked, extracellular transretinal electroretinogram (ERG), and ON and OFF retinal ganglion cell (RGC) field excitatory postsynaptic potential (fEPSP) responses from the acutely isolated, dark-adapted, mouse retina. Alterations to microglial morphology, under similar conditions, were also explored. Initial experiments confirmed the excitatory responses as predominantly mediated via the ‘classic’ rod photoreceptor – rod-ON bipolar cell – AII amacrine cell pathway. With the use of selective P2X7R antagonists, it was shown that P2X7R activation directly modulated photoreceptor, ON bipolar cell and ON RGC function, but not OFF RGC function, through partially independent mechanisms. A novel finding of this study demonstrated that acute application of the microglia-activating bacterial component, lipopolysaccharide (LPS) modulated inner retinal function, possibly through a P2X7R- and Pannexin-1-associated mechanism of microglial ATP release. These results were supported by observations of early morphometric changes to microglia caused by P2X7R activation and LPS, as revealed by immunofluorescence labelling and confocal laser scanning microscopy. Since changes in neurotransmission and microglial function are early indicators of neuropathology, these results contribute to the understanding of early neural-immune interactions in retinal disease, and in the central nervous system as a whole.

Type: Thesis (Doctoral)
Title: P2X7 Receptor Modulation of Visual Responses in the Retina
Open access status: An open access version is available from UCL Discovery
Language: English
Keywords: P2X7 receptor, Retina, Retinal ganglion cell, Microglia, Electroretinogram (ERG), fEPSP, Retinal wholemount, BzATP, Lipopolysaccharide
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/1464069
Downloads since deposit
287Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item