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D.-Q. Zhang, T.-R. Zhou, D. G. McMahon; Structural and Functional Preservation of Dopaminergic Amacrine Cells in Retinal Degeneration. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5684.
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© ARVO (1962-2015); The Authors (2016-present)
Loss of photoreceptors in retinal degenerative diseases such as retinitis pigmentosa is thought to cause morphological and functional abnormalities of inner retinal neurons. Dopaminegic amacrine (DA) cells, a class of inner retinal neurons, play key roles in retinal development, visual processing and tropic effects in the vertebrate retina. It is unknown whether DA cell morphology and physiology are preserved after the loss of photoreceptors. In this study, we sought to examine the structure and function of DA cells in retinal degeneration (rd1) mouse.
Loose-patch and whole-cell recordings were made from soma of red fluorescence protein (RFP) labeled cells visualized with epi-fluorescence microscopy in the retinas of rd1 tyrosine hydroxylase driven RFP transgenic mice. DA cells were stained with an antibody against tyrosine hydroxylase in whole-mount retinas.
(1) The total number of DA cells remained unchanged in the rd1 retina. The average area of individual somata decreased from 149 µm2 (n=94) in the wild-type (WT) retina to 101 µm2 (n=68) in the rd1 retina. The results suggest that DA cells are morphologically intact with shrinkage of the cell body. (2) The loss of photoreceptors did not change the spontaneous firing rate of DA cells, but decreased the percentage of spikes within bursts from 61% (n=6) in the WT retina to 25% (n=7) in the rd1 retina, suggesting that rd1-DA cells remain firing spontaneously, but in an irregular single-spike pattern. (3) Bicuculline, a GABAA receptor antagonist, depolarized DA cells and produced rhythmic bursts of spikes (n=2), suggesting rd1-DA cells are inhibited by GABAergic amacrine cells in darkness. (4) L-AP4 and CNQX depolarized DA cells and increased their firing rate in the rd1 retina, respectively (n=4), suggesting that depolarization of ON bipolar cells caused by the loss of photoreceptors inhibits DA cells through activation of GABAergic amacrine cells. (5) Light depolarized a majority of rd1-DA cells with an increase of firing rate during and 10-30 seconds after illumination. The light-induced response of DA cells was blocked by CNQX (n=2). The results indicate that synaptic input from melanopsin ganglion cell photoreceptors is preserved in the rd1 retina.
Our results indicate the morphology and physiology of DA cells are partially preserved after the loss of rod/cone photoreceptors. DA cells are inhibited by GABAergic amacrine cells in darkness, and excited by glutamatergic melanopsin ganglion cell photoreceptors upon light stimulation. The preservation of the dopaminergic system may have a potential impact on maintaining the inner retinal circuits in retinal degeneration.
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