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Ralph J Jensen; Effects of blocking GABA-C and mGlu1 receptors on contrast response functions of retinal ganglion cells in P23H rat. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2584. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Previous studies have shown that blocking GABA-C and mGlu1 receptors increase sensitivity of retinal ganglion cells (RGCs) in the P23H rat (a model of retinitis pigmentosa) to flashes of light. Here I examined the effects of blockers of these receptors on the contrast response functions of RGCs in P23H rat retina.
Following euthanasia of a rat with sodium pentobarbital, an eye was removed and hemisected. A square piece of retina was cut out and transferred with the ganglion cell side down onto a 64-channel planar Muse MEA (Axion Biosystems). A gravity-flow system provided carboxygenated Ames' Medium to the retina. The visual stimulus was a drifting sinusoidal grating (spatial frequency: 1 cycle/mm; temporal frequency: 2 cycles/s) that varied in stimulus contrast. The mean stimulus illuminance was held constant at 15 lux. Sorted spikes from RGCs were imported into Neuroexplorer software to create post-stimulus time histograms, averaged across 7 repetitions of the same contrast. Each histogram was Fourier transformed with OriginPro10 software to obtain the amplitude of the fundamental stimulus frequency (F1). Data were obtained before and during bath application of either the GABA-C receptor antagonist TPMPA (100 μM) or the mGlu1 receptor antagonist JNJ16259685 (0.5 μM).
I have examined the effects of TPMPA and JNJ16259685 on the contrast response functions of over 80 P23H rat RGCs. I found that the effects of both TPMPA and JNJ16259685 were similar, in that these antagonists increased the responses of RGCs at all stimulus contrast levels. This is illustrated in the figure for one RGC that was treated with TPMPA. The data points fitted with the solid line are control values; the data points fitted with the dash line are values obtained in presence of TPMPA. For this cell, and many other cells, TPMPA and JNJ16259685 caused the curve to shift mainly vertically (i.e. an increase in response gain) rather than horizontally (i.e. an increase in contrast gain). Taking the F1 amplitude of 4 spikes/s as contrast threshold, I found that both TPMPA and JNJ16259685 significantly decreased (p<0.01) contrast thresholds of the RGCs.
Blocking either GABA-C or mGlu1 receptors improves the contrast response functions of RGCs in an animal model of retinitis pigmentosa.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
Effect of TPMPA on contrast response function of a P23H rat RGC
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