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Narender K. Dhingra, Abhinaba Ghosh; Loss of Photoreceptors in rd1 Mouse is Associated with Upregulation of GABAC Receptors in Inner Retina. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4656.
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© ARVO (1962-2015); The Authors (2016-present)
Loss of photoreceptors in retinal degenerative diseases leads to significant morphological and physiological changes in inner retina, which have implications for developing novel therapeutic strategies for these diseases. We previously found that photoreceptor loss results in increased levels of amacrine cell-specific synaptic proteins, implying increased synaptic activity in these cells. However, the mechanism underlying this change and its consequences for inner retina are unclear. The increased activity in the predominantly inhibitory amacrine cells should lead to increased inhibition of bipolar and ganglion cells, potentially contributing to generation of the aberrant firing patterns observed in ganglion cells after photoreceptor loss. Here, we asked whether increased activity in GABAergic amacrine cells in rd1 mouse results in upregulation of GABAC receptors on bipolar cell terminals.
Retinas from adult, wildtype (C57BL/6J) and rd1 (CBA/J) mice were immunolabeled for ρ subunits of GABAC receptor. The staining intensity was plotted against the antibody dilution (range: 10x to 10000x) to find the linear range, and a 100x dilution was used for the experiments reported here. Images were acquired by confocal microscopy and analyzed by ImageJ software. Intensity of GABAC immunofluorescence in the inner plexiform (IPL) layer was quantified as a measure of the receptor density.
The intensity of GABAC staining in the IPL of rd1 mouse (13.7±4.4) was nearly twice that in the wildtype mouse (7.2±2.8), implying higher receptor density (t-test; p<0.05; n=4).
Our findings that synaptic activity in amacrine cells is increased and GABAC receptors in IPL are upregulated in rd1 mouse retina, suggest that loss of photoreceptors results in increased GABAC-mediated feedback inhibition of the bipolar cells.
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