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Seetal Chavda, Philip J Luthert, Thomas E Salt; P2X7 receptors modulate outer retinal and retinal ganglion cell synaptic responses in the ex vivo mouse retina. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2246.
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© ARVO (1962-2015); The Authors (2016-present)
P2X7R activation is known to modulate mouse electroretinogram (ERG) responses in vivo, as well as driving photoreceptor and retinal ganglion cell (RGC) damage, a consequence of various neurodegenerative conditions. However, the complexity that P2X7Rs are distributed throughout all layers of the retina, and their localisation on various cell types puts into question their specific site(s) of action. Using a dark-adapted, ex vivo mouse retinal wholemount preparation, the present study aimed to characterise the effect of P2X7R activation on light-evoked outer retinal responses, and on RGC synaptic responses in the inner retina, under comparable conditions.
ERG responses were recorded from the surface of isolated retinal wholemounts (adult, female C57BL/6 mice) in response to a light stimulus (1s-duration, peak wavelength 562nm, repeated every 3s). In separate experiments, ON field excitatory post-synaptic potentials (fEPSPs) were recorded from the ganglion cell layer wholemounts. The NMDAR-mediated component of the responses was isolated with a Mg2+-free Krebs medium containing NBQX, picrotoxin, strychnine and tetrodotoxin. Additional compounds were applied to the bathing medium.
In physiological Krebs medium, BzATP (300µM), a P2XR agonist, induced a marked potentiation of the ERG a-wave slope to 149.0±14% of control with a concomitant reduction in the b-wave amplitude to 80.6±4% of control (both P<0.05 vs. control, n=7). BzATP also reduced the power of the ERG oscillatory potentials. In the pharmacologically modified, Mg2+-free perfusate, BzATP reduced both the a-wave slope (70.1±8% of control) and b-wave amplitude (66.6±10% of control; both P<0.05 vs. control, n=7). The effect of BzATP on the ERG components were markedly reduced by the selective P2X7R antagonist, A438079 (10µM; a-wave: 4±16% of control; b-wave: 58.3±16% of control; both P<0.05, n=7). The ON RGC fEPSP was reduced in the presence of BzATP (78±2% of control; P<0.0001, n=21), an effect which was significantly attenuated by A438079 (68.7 ±2% of control; P<0.05, n=6).
In summary, P2X7R modulates the photoreceptor response, ON-bipolar cell output and ON-retinal ganglion cell responses through partially independent mechanisms. Understanding the physiological role of P2X7Rs in synaptic signalling may provide clues as to how these ‘danger-sensors’ contribute to neuronal dysfunction.
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