Glutamate Stimulation of Retinal Ganglion Cells in Normal and S334ter-4 Rat Retinas: A Candidate for a Neurotransmitter-Based Retinal Prosthesis
Glutamate Stimulation of Retinal Ganglion Cells in Normal and S334ter-4 Rat Retinas: A Candidate for a Neurotransmitter-Based Retinal Prosthesis
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DOI：
10.1167/iovs.09-4877
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发表时间：
2010-07-01
影响因子：
4.4
通讯作者：
Iezzi, Raymond
中科院分区：
文献类型：
--
作者：
Finlayson, Paul G.;Iezzi, Raymond
目的。研究谷氨酸作为神经递质视网膜假体的潜在药物的适用性。将P35-70白化Sprague-Dawley（正常）大鼠和P60-254 S334ter-4（光感受器变性）大鼠的视网膜神经节细胞（RGCs）记录在扁平的眼杯中，通过微移液管观察其对谷氨酸的反应。谷氨酸在正常视网膜和变性视网膜的局部应用可有效激活RGCs。谷氨酸在视网膜表面的应用比在视网膜表面下（视网膜表面以下20 μ m）的应用更不容易激发RGCs。谷氨酸引起RGC放电率，并且在视网膜表面和表面下应用的反应模式相似。2 mM谷氨酸在表面下有效地刺激了130 μ m内的细胞。在正常视网膜中，关闭RGCs的反应潜伏期平均为281 ms，明显长于打开RGCs （P = 0.025）。在大多数自发活动的rgc中，谷氨酸应用后，活性抑制在较短的潜伏期（类似于100 ms）被观察到。对每种谷氨酸的反应是相似的，活性的持续时间直接取决于应用的持续时间。在正常视网膜和退化视网膜中，RGC的反应各不相同，从反复的高频脉冲到持续的超过40峰值/秒的放电。成对的，连续的谷氨酸应用诱发了两种可区分的反应，刺激间隔低至200毫秒。总体而言，RGC对谷氨酸的反应敏感性在正常视网膜和变性视网膜中相似。谷氨酸是基于神经递质的视网膜假体的优秀候选者，因为它的局部应用可以有效地刺激RGCs，具有高空间和时间分辨率。（Invest Ophthalmol Vis Sci. 2010;51:3619-3628） DOI: 10.1167/iovs.09-4877
PURPOSE. To investigate the suitability of glutamate as a potential agent for a neurotransmitter-based retinal prosthesis.METHODS. Retinal ganglion cells (RGCs) from P35-70 albino Sprague-Dawley (normal) and P60-254 S334ter-4 (photoreceptor degeneration) rats were recorded extracellularly in flattened eye cup preparations, to assess their responses to glutamate, applied locally via micropipettes.RESULTS. Brief local application of glutamate effectively excited RGCs in both normal and degenerated retinas. Epiretinal surface application of glutamate was less likely to excite RGCs than was subsurface application (20 mu m below the epiretinal surface). Glutamate evoked RGC firing rates, and the response patterns were similar for epiretinal surface and subsurface applications. Subsurface application of 2 mM glutamate effectively excited cells within 130 mu m of the ejection sites. Response latencies averaged 281 ms and were significantly longer for OFF RGCs than for ON RGCs in normal retinas (P = 0.025). Suppression of activity was observed at shorter latencies (similar to 100 ms) after glutamate application in most of the spontaneously active RGCs. Responses to each glutamate application were similar, and the duration of activity was directly dependent on the duration of application. RGC responses varied from recurrent high-frequency bursts to sustained firing at rates above 40 spikes/s, in normal and degenerated retinas. Paired, sequential applications of glutamate evoked two distinguishable responses, with interstimulus intervals as low as 200 ms. Overall, RGC response sensitivity to glutamate was similar in normal and degenerated retinas.CONCLUSIONS. Glutamate is an excellent candidate for a neurotransmitter-based retinal prosthesis, as its local application effectively stimulates RGCs with high spatial and temporal resolution. (Invest Ophthalmol Vis Sci. 2010;51:3619-3628) DOI: 10.1167/iovs.09-4877