Microfluidics-Based Subretinal Chemical Neuromodulation of Photoreceptor Degenerated Retinas.
Microfluidics-Based Subretinal Chemical Neuromodulation of Photoreceptor Degenerated Retinas.
复制标题
基于微流体的视网膜下化学神经调节光感受器退化视网膜。
DOI：
10.1167/iovs.17-23142
复制
发表时间：
2018
影响因子：
4.4
通讯作者：
L. Saggere
中科院分区：
文献类型：
--
作者：
Corey M. Rountree;J. Troy;L. Saggere
目的
视网膜假体可以通过电刺激在光感受器退化的情况下恢复基本的视力，但是面临实现高空间分辨率的困难，因为电流是固有的非自然刺激。我们研究了使用谷氨酸神经递质的模式化递送的治疗可行性，谷氨酸神经递质是视网膜的天然突触通信的主要试剂，作为电流的仿生化学替代物，用于光感受器退化视网膜的神经调节。
方法
我们使用玻璃微量移液器和原型多端口微流控装置将少量神经递质谷氨酸注射到20只视网膜下的光感受器变性的S334 ter-3大鼠视网膜中，以完成体外单位点和多位点刺激。化学刺激的影响，其特征在于使用多电极阵列记录视网膜神经节细胞（RGC）的神经反应。
结果
视网膜下注射外源性谷氨酸激活RGCs，尽管视网膜重塑引起了实质性的解剖和生理变化，引发了强大的神经反应。兴奋性和抑制性RGC反应的存在提供了证据表明，外源性谷氨酸差异激活神经元突触前的RGC，可能是内部视网膜神经元属于OFF和ON途径。我们还证明，谷氨酸注射可以引起局灶性RGC反应，其空间分辨率与当前一代电假体相当或更好，并且当与多端口微流体装置同时应用于多个部位时，可以产生空间图案化的神经反应。
结论
这些重要的结果表明，用神经递质对变性视网膜进行化学刺激是一种有效的神经调节策略，具有恢复因光感受器变性而失明的患者的高分辨率视觉感知的潜力。
Purpose
Retinal prostheses can restore rudimentary vision in cases of photoreceptor degeneration through electrical stimulation, but face difficulties achieving high spatial resolution because electrical current is an inherently unnatural stimulus. We investigated the therapeutic feasibility of using patterned delivery of the glutamate neurotransmitter, a primary agent of natural synaptic communication of the retina, as a biomimetic chemical alternative to electrical current for neuromodulation of photoreceptor degenerate retina.
Methods
We injected small quantities of the neurotransmitter glutamate into the subretina of 20 explanted photoreceptor degenerated S334ter-3 rat retinas using glass micropipettes and a prototype multiport microfluidic device to accomplish single- and multisite stimulation in vitro. The effects of chemical stimulation were characterized by recording neural responses from retinal ganglion cells (RGCs) using a multielectrode array.
Results
Subretinally injected exogenous glutamate activates RGCs, despite the substantial anatomic and physiologic changes caused by retinal remodeling, eliciting robust neural responses. The presence of excitatory and inhibitory RGC responses provides evidence that exogenous glutamate differentially activated neurons presynaptic to RGCs, likely inner retinal neurons belonging to the OFF and ON pathways. We also demonstrate that glutamate injections can evoke focal RGC responses with spatial resolutions comparable to or better than current generation electrical prostheses and, when applied at multiple sites simultaneously with the multiport microfluidic device, can produce spatially patterned neural responses.
Conclusions
These significant results establish that chemical stimulation of degenerated retinas with neurotransmitters is an effective neuromodulation strategy with the potential of restoring high-resolution visual perception in patients rendered blind through photoreceptor degeneration.
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DOI：
10.1146/annurev-genom-090413-025610
发表时间：
2014
影响因子：
8.7
作者：
Fritsche LG;Fariss RN;Stambolian D;Abecasis GR;Curcio CA;Swaroop A
通讯作者：
Swaroop A
影响因子：
1.8
作者：
Zrenner, E;Stett, A;Haemmerle, H
通讯作者：
Haemmerle, H
影响因子：
3.4
作者：
Martinez-Navarrete, G.;Seiler, M. J.;Aramant, R. B.;Fernandez-Sanchez, L.;Pinilla, I.;Cuenca, N.
通讯作者：
Cuenca, N.
眼内视网膜移植。
影响因子：
4.4
作者：
delCerro,M;Gash,DM;Rao,GN;Notter,MF;Wiegand,SJ;Gupta,M
通讯作者：
Gupta,M
影响因子：
4.4
作者：
Finlayson, Paul G.;Iezzi, Raymond
通讯作者：
Iezzi, Raymond