Impact of Retinal Degeneration on Response of ON and OFF Cone Bipolar Cells to Electrical Stimulation.
Impact of Retinal Degeneration on Response of ON and OFF Cone Bipolar Cells to Electrical Stimulation.
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DOI：
10.1109/tnsre.2023.3276431
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发表时间：
2023
影响因子：
4.9
通讯作者：
Lazzi, Gianluca
中科院分区：
文献类型：
--
作者：
Farzad, Shayan;Kosta, Pragya;Iseri, Ege;Walston, Steven T.;Bouteiller, Jean-Marie C.;Pfeiffer, Rebecca L.;Sigulinsky, Crystal L.;Yang, Jia-Hui;Garcia, Jessica C.;Anderson, James R.;Jones, Bryan W.;Lazzi, Gianluca
关键词：
在视网膜变性疾病中，例如视网膜色素变性（RP）和年龄相关性黄斑变性（AMD），光感受器在疾病的早期阶段变得紧张并开始退化。视网膜修复装置已经被开发出来，通过对存活的视网膜细胞施加电刺激来恢复患者的视力。然而，这些装置提供有限的视觉感知，因为治疗干预通常在仅留下视网膜内层细胞的疾病的后期阶段被考虑。早期阶段视网膜退行性疾病的潜在治疗选择可以是刺激双极细胞，其接收来自光感受器的突触前信号。在这项工作中，我们构建了健康和退化（ON和OFF型）锥双极细胞（CBCs）的计算模型，从健康和早期退化的兔视网膜的连接体中提取逼真的形态。我们研究了这些细胞的膜电位和轴突终末钙电流的差异时，受到电刺激。此外，我们研究了健康和退化细胞在各种刺激参数方面的不同表现，包括脉冲持续时间和细胞与刺激电极的距离。结果表明，无论OFF CBCs在视网膜模型中的位置如何，当电刺激时，健康和退化细胞的膜电位之间没有显著差异。而健康ON CBC轴突终末膜电位上升时间常数（0.29 ± 0.03 ms）较变性细胞（0.8 ± 0.07 ms）短。此外，在细胞轴突末端的离子钙通道具有更高的浓度和更高的电流在退化的细胞（32.24 ± 6.12 pA）比健康的细胞（13.64 ± 2.88 pA）独立于细胞的位置。
In retinal degenerative diseases, such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD), the photoreceptors become stressed and start to degenerate in the early stages of the disease. Retinal prosthetic devices have been developed to restore vision in patients by applying electrical stimulation to the surviving retinal cells. However, these devices provide limited visual perception as the therapeutic interventions are generally considered in the later stages of the disease when only inner retinal layer cells are left. A potential treatment option for retinal degenerative diseases in the early stages can be stimulating bipolar cells, which receive presynaptic signals from photoreceptors. In this work, we constructed computational models of healthy and degenerated (both ON and OFF-type) cone bipolar cells (CBCs) with realistic morphologies extracted from connectomes of the healthy and early-stage degenerated rabbit retina. We examined these cells’ membrane potential and axon terminal calcium current differences when subjected to electrical stimulation. In addition, we investigated how differently healthy and degenerated cells behave with respect to various stimulation parameters, including pulse duration and cells’ distance from the stimulating electrode. The results suggested that regardless of the position of the OFF CBCs in the retina model, there is not a significant difference between the membrane potential of healthy and degenerate cells when electrically stimulated. However, the healthy ON CBC axon terminal membrane potential rising time-constant is shorter (0.29 ± 0.03 ms) than the degenerated cells (0.8 ± 0.07 ms). Moreover, the ionic calcium channels at the axon terminals of the cells have a higher concentration and higher current in degenerated cells (32.24 ± 6.12 pA) than the healthy cells (13.64 ± 2.88 pA) independently of the cell’s position.
影响因子：
4
作者：
Freeman DK;Jeng JS;Kelly SK;Hartveit E;Fried SI
通讯作者：
Fried SI
影响因子：
1.2
作者：
Maturana, Matias I.;Kameneva, Tatiana;Burkitt, Anthony N.;Meffin, Hamish;Grayden, David B.
通讯作者：
Grayden, David B.
哺乳动物内视网膜中间隙连接连接的区域变化。
影响因子：
6
作者：
Fusz K;Kovács-Öller T;Kóbor P;Szabó-Meleg E;Völgyi B;Buzás P;Telkes I
通讯作者：
Telkes I