Network-mediated responses of ON ganglion cells to electric stimulation change over the course of retinal degeneration

Network-mediated responses of ON ganglion cells to electric stimulation change over the course of retinal degeneration
임매순이재익Shelley Fried
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The Association for Research in Vision and Ophthalmology (ARVO)
Purpose : Microelectronic retinal prostheses have been used to restore sight in individuals with profound vision loss caused by outer retinal degenerative diseases. Previously, we reported in the healthy retina that some components of electrically-elicited responses in ON types of retinal ganglion cells (RGCs) resemble the corresponding components of visually-elicited responses. However, it is not known whether such similarities persist as the retina degenerates and so here we studied how responses change over the course of time in rd10 mice. Methods : Cell-attached patch clamp was used to record spikes from RGCs in retinal explants from rd10 mice, a slow degeneration model of retinitis pigmentosa. Alpha RGCs were targeted by their large soma (>20 &micro; m) and classified as ON or OFF by their response to stationary flashes. After classification, a monophasic half-sinusoidal wave (4 ms duration, -100 &micro; A amplitude) was delivered epiretinally to elicit network-mediated responses. Each stimulus was repeated 7 times. We recorded the spiking activity in ON RGCs from retinas at postnatal days 15 (n=9), 31 (n=9) and 60 (n=4). Results : Network-mediated responses in ON alpha RGCs varied systematically with age. 1) The peak firing rate decreased as retinal degeneration progressed: 148.3±65.2 Hz, 79.2±35.7 Hz (p=0.008) and 17.1±16.2 Hz (p<0.001) at P15, 31 and 60, respectively. 2) The latency at which peak firing occurred increased as degeneration progressed: latencies to peak firing were 161±40 ms, 224±112 ms (p=0.073) and 536±309 ms (p=0.047) at P15, P31 and P60, respectively. Conclusions : Sharp changes in peak firing rate and latency were observed over the course of degeneration and should be taken into consideration during the development of stimulation strategies that activate the retinal network. Because bipolar cells are thought to remain intact through P60 and beyond, our results suggest that they becom
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