Retinal ganglion cells undergo cell type-specific functional changes in a computational model of cone-mediated retinal degeneration.
Retinal ganglion cells undergo cell type-specific functional changes in a computational model of cone-mediated retinal degeneration.
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DOI：
10.3389/fnins.2023.1147729
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发表时间：
2023
影响因子：
4.3
通讯作者：
Beyeler, Michael
中科院分区：
文献类型：
--
作者：
Xu, Aiwen;Beyeler, Michael
了解健康和疾病中的视网膜是神经科学和神经工程应用（例如视网膜假体）的关键问题。在变性过程中，视网膜网络经历复杂的多阶段神经解剖学改变，这极大地影响了视网膜神经节细胞（RGC）的反应，具有临床重要性。在这里，我们提出了视网膜中锥体通路的生物物理详细计算机模型，该模型模拟对光和电刺激的网络级响应。该模型包括 11, 138 个细胞，属于 9 种不同的细胞类型（视锥细胞、水平细胞、ON/OFF 双极细胞、ON/OFF 无长突细胞和 ON/OFF 神经节细胞），这些细胞局限于中心凹旁视网膜的 300 × 300 × 210μm 斑块内。在验证该模型再现了有关视网膜神经节细胞（RGC）光反应的开创性发现后，我们系统地向网络引入了解剖学和神经生理学变化（例如，光感受器的光敏感性降低、细胞死亡、细胞迁移），并研究了它们对网络活动的影响。该模型不仅能够重现退化视网膜中 RGC 活动的常见发现，例如活动过度和电阈值增加，而且还提供了有关潜在神经解剖机制的可测试预测。总体而言，我们的研究结果表明，以视锥细胞介导的视网膜变性为代表的生物物理变化可能如何影响视网膜对光和电刺激的反应。这些见解可能会进一步加深我们对视网膜处理的理解，并为视网膜假体的设计提供信息。
Understanding the retina in health and disease is a key issue for neuroscience and neuroengineering applications such as retinal prostheses. During degeneration, the retinal network undergoes complex and multi-stage neuroanatomical alterations, which drastically impact the retinal ganglion cell (RGC) response and are of clinical importance. Here we present a biophysically detailed in silico model of the cone pathway in the retina that simulates the network-level response to both light and electrical stimulation. The model included 11, 138 cells belonging to nine different cell types (cone photoreceptors, horizontal cells, ON/OFF bipolar cells, ON/OFF amacrine cells, and ON/OFF ganglion cells) confined to a 300 × 300 × 210μm patch of the parafoveal retina. After verifying that the model reproduced seminal findings about the light response of retinal ganglion cells (RGCs), we systematically introduced anatomical and neurophysiological changes (e.g., reduced light sensitivity of photoreceptor, cell death, cell migration) to the network and studied their effect on network activity. The model was not only able to reproduce common findings about RGC activity in the degenerated retina, such as hyperactivity and increased electrical thresholds, but also offers testable predictions about the underlying neuroanatomical mechanisms. Overall, our findings demonstrate how biophysical changes typified by cone-mediated retinal degeneration may impact retinal responses to light and electrical stimulation. These insights may further our understanding of retinal processing and inform the design of retinal prostheses.
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影响因子：
3.7
作者：
Margolis DJ;Gartland AJ;Singer JH;Detwiler PB
通讯作者：
Detwiler PB
影响因子：
4
作者：
Guo, Tianruo;Tsai, David;Dokos, Socrates
通讯作者：
Dokos, Socrates
DOI：
10.1109/tnsre.2018.2832055
发表时间：
2018-06-01
影响因子：
4.9
作者：
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通讯作者：
Lazzi, Gianluca
影响因子：
5.3
作者：
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通讯作者：
Senok SS
影响因子：
2.5
作者：
Fohlmeister, JF;Miller, RF
通讯作者：
Miller, RF