Feasibility study for a glutamate driven subretinal prosthesis: local subretinal application of glutamate on blind retina evoke network-mediated responses in different types of ganglion cells
Feasibility study for a glutamate driven subretinal prosthesis: local subretinal application of glutamate on blind retina evoke network-mediated responses in different types of ganglion cells
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DOI：
10.1088/1741-2552/aac811
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发表时间：
2018-08-01
影响因子：
4
通讯作者：
Zrenner, Eberhart
中科院分区：
文献类型：
--
作者：
Haq, Wadood;Dietter, Johannes;Zrenner, Eberhart
目标。介绍了一种基于传输器的视网膜下假体的可行性研究，该假体可以在盲鼠视网膜上产生视觉反应。接近。用局部谷氨酸(Glu)或N-甲基-D-天冬氨酸(NMDA)通过微管(约1.5µm)刺激变性Rd1小鼠视网膜，用钙显像法记录视网膜外部活动，用多电极阵列系统记录档案神经节细胞(GC)活动。Glu受体阻断剂的应用证实了双极细胞通过网络介导的GC激活。主要结果。变性和失明的Rd1小鼠视网膜的数据显示，视网膜外部是Glu敏感的，视网膜下Glu刺激促进了网络介导的GC反应。空间活动扩散分析表明，Glu诱导的视网膜外层细胞激活半径(类似于12.5微米)和突触后激活的GC(类似于40微米)集中在刺激顶端。此外，NMDA在视网膜下腔的应用也引起了网络介导的GC反应。Glu激活的GC被鉴定为ON-OFF、OFF和两种ON细胞类型。意义重大。这项研究评估了基于递质的植入物功能的先决条件，即在失去光感受器后，残留的盲目视网膜网络是Glu敏感的和积极的功能。递质Glu对ON(超极化)和OFF(去极化)双极细胞的不同激活是视网膜植入物的一个独特特征和高度关注的问题。因此，相应的双极细胞类型只能由谷氨酸能刺激准确驱动，而不能由电刺激驱动。在完全失明的情况下，失明视网膜的功能被保留下来，这促使人们继续研究基于传输器的假体。由于人工Glu刺激模拟了自然的视网膜输入，由于神经元的可塑性，早期植入Glu假体可能会积极地推迟破坏性的视网膜重塑。
Objective. A feasibility study for a transmitter based subretinal prosthesis, generating visual responses in blind mouse retina is presented. Approach. Degenerated rd1 mouse retina were stimulated in subretinal configuration by local glutamate (Glu) or NMDA application via micropipettes (similar to 1.5 mu m) and thereby the outer retinal activity was recorded by calcium-imaging or file ganglion cell (GC) activity was recorded by the multi-electrode array system. The network mediated activation of GC via bipolar cells was approved by the administration of Glu receptor blockers. Main results. Data of the degenerated and blind rd1 mouse retina reveals that the outer retina is Glu sensitive and that the subretinal Glu stimulation promotes network mediated GC responses. Analysis of the spatial activity-spread indicates that the Glu induced cell activation radius in the outer retina (similar to 12.5 mu m) and postsynaptically activated GC (similar to 40 mu m) is focal to the stimulation pipette tip. Moreover, the application of NMDA in subretinal space also evoked network mediated GC responses. The Glu-activated GC were identified as ON-OFF, OFF and two ON cells types. Significance. This study evaluates the prerequisite for the function of a transmitter based implant, that after the loss of the photoreceptors, the remnant blind retinal network is Glu sensitive and functional, positively. The differential activation of ON (hyperpolarisation) and OFF (depolarisation) bipolar cells by transmitter Glu is a unique feature and of high interest for retinal implants. Therefore, the respective bipolar cell types could only be driven by glutamatergic stimulation accurately and not by electrical stimulation. The preserved functionality of the blind retina at the onset of complete blindness is motivating to continue research on a transmitter-based prosthesis. Since the artificial Glu stimulation mimics the natural retinal input, early implantation of a Glu-prosthesis might delay the devastating retinal remodelling positively, due to the neuronal-plasticity.