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光遗传学策略在视力恢复中的应用。

Optogenetic Strategies for Vision Restoration.

机构信息

Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI, USA.

出版信息

Adv Exp Med Biol. 2021;1293:545-555. doi: 10.1007/978-981-15-8763-4_38.

DOI:10.1007/978-981-15-8763-4_38
PMID:33398841
Abstract

The loss of photoreceptor cells caused by retinal degenerative diseases leads to blindness. The optogenetic approach for restoring vision involves converting the surviving inner retinal neurons into photosensitive cells, thus imparting light sensitivity to the retina following the loss of photoreceptor cells. Our first demonstration of the feasibility of such an approach involved expressing ChR2 in the retinal ganglion cells of blind mice; since then, optogenetic vision restoration has been demonstrated by using a variety of optogenetic tools, especially microbial channelrhodopsins (ChRs). A ChR-based optogenetic therapy for treating blindness has advanced to clinical trials. In this chapter, we review our early proof-of-concept study of optogenetic vision restoration. We also discuss our studies for developing better ChR tools and for restoring intrinsic visual processing features in retinas with degenerated photoreceptors.

摘要

视网膜退行性疾病引起的光感受器细胞丧失会导致失明。光遗传学恢复视力的方法包括将存活的内视网膜神经元转化为光敏感细胞,从而在光感受器细胞丧失后赋予视网膜光敏感性。我们首次证明了这种方法的可行性,即将 ChR2 表达在盲鼠的视网膜神经节细胞中;此后,通过使用各种光遗传学工具,特别是微生物通道视紫红质(ChRs),已经证明了光遗传学视觉恢复。基于 ChR 的光遗传学疗法已进入临床试验阶段。在本章中,我们回顾了我们关于光遗传学视觉恢复的早期概念验证研究。我们还讨论了我们在开发更好的 ChR 工具以及恢复具有退行性光感受器的视网膜内在视觉处理特征方面的研究。

相似文献

1
Optogenetic Strategies for Vision Restoration.光遗传学策略在视力恢复中的应用。
Adv Exp Med Biol. 2021;1293:545-555. doi: 10.1007/978-981-15-8763-4_38.
2
rAAV-mediated subcellular targeting of optogenetic tools in retinal ganglion cells in vivo.体内活体视网膜神经节细胞中光遗传工具的 rAAV 介导的亚细胞靶向。
PLoS One. 2013 Jun 14;8(6):e66332. doi: 10.1371/journal.pone.0066332. Print 2013.
3
Improved CoChR Variants Restore Visual Acuity and Contrast Sensitivity in a Mouse Model of Blindness under Ambient Light Conditions.在环境光照条件下,改良的 CoChR 变体可恢复盲鼠模型的视力和对比敏感度。
Mol Ther. 2019 Jun 5;27(6):1195-1205. doi: 10.1016/j.ymthe.2019.04.002. Epub 2019 Apr 9.
4
Ectopic expression of a microbial-type rhodopsin restores visual responses in mice with photoreceptor degeneration.微生物型视紫红质的异位表达可恢复光感受器退化小鼠的视觉反应。
Neuron. 2006 Apr 6;50(1):23-33. doi: 10.1016/j.neuron.2006.02.026.
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A New Promoter Allows Optogenetic Vision Restoration with Enhanced Sensitivity in Macaque Retina.新型启动子可增强灵长类动物视网膜中的光遗传学视觉恢复敏感性。
Mol Ther. 2017 Nov 1;25(11):2546-2560. doi: 10.1016/j.ymthe.2017.07.011. Epub 2017 Jul 20.
6
Functional Availability of ON-Bipolar Cells in the Degenerated Retina: Timing and Longevity of an Optogenetic Gene Therapy.变性视网膜中 ON-双极细胞的功能可用性:光遗传学基因治疗的时机和持久性。
Int J Mol Sci. 2021 Oct 26;22(21):11515. doi: 10.3390/ijms222111515.
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Optogenetics for visual restoration: From proof of principle to translational challenges.光遗传学在视觉修复中的应用:从原理验证到转化挑战。
Prog Retin Eye Res. 2022 Nov;91:101089. doi: 10.1016/j.preteyeres.2022.101089. Epub 2022 Jun 9.
8
Optogenetic Approaches to Restoring Vision.恢复视力的光遗传学方法。
Annu Rev Vis Sci. 2015 Nov 24;1:185-210. doi: 10.1146/annurev-vision-082114-035532.
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Optogenetic Therapy for Visual Restoration.光遗传学疗法治疗视觉恢复。
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Visual function in mice with photoreceptor degeneration and transgenic expression of channelrhodopsin 2 in ganglion cells.感光细胞变性小鼠和转染表达通道视紫红质 2 的神经节细胞的视觉功能。
J Neurosci. 2010 Jun 30;30(26):8745-58. doi: 10.1523/JNEUROSCI.4417-09.2010.

引用本文的文献

1
Differential Impact of Retinal Lesions on Visual Responses of LGN X and Y Cells.视网膜病变对外侧膝状体X和Y细胞视觉反应的差异影响。
J Neurosci. 2025 Jun 4;45(23):e0436252025. doi: 10.1523/JNEUROSCI.0436-25.2025.
2
Intravitreally Injected Plasmonic Nanorods Activate Bipolar Cells with Patterned Near-Infrared Laser Projection.玻璃体内注射的等离子体纳米棒通过图案化近红外激光投影激活双极细胞。
ACS Nano. 2025 Apr 1;19(12):11823-11840. doi: 10.1021/acsnano.4c14061. Epub 2025 Mar 20.
3
Theoretical prediction of broadband ambient light optogenetic vision restoration with ChRmine and its mutants.

本文引用的文献

1
Improved CoChR Variants Restore Visual Acuity and Contrast Sensitivity in a Mouse Model of Blindness under Ambient Light Conditions.在环境光照条件下,改良的 CoChR 变体可恢复盲鼠模型的视力和对比敏感度。
Mol Ther. 2019 Jun 5;27(6):1195-1205. doi: 10.1016/j.ymthe.2019.04.002. Epub 2019 Apr 9.
2
Restoration of high-sensitivity and adapting vision with a cone opsin.用视蛋白恢复高灵敏度和适应视觉。
Nat Commun. 2019 Mar 15;10(1):1221. doi: 10.1038/s41467-019-09124-x.
3
A Robust Optomotor Assay for Assessing the Efficacy of Optogenetic Tools for Vision Restoration.
理论预测 ChRmine 和其突变体的宽带环境光基因光学视力恢复。
Sci Rep. 2024 May 21;14(1):11642. doi: 10.1038/s41598-024-62558-2.
4
Ion Channels and Transporters as Therapeutic Agents: From Biomolecules to Supramolecular Medicinal Chemistry.作为治疗剂的离子通道和转运体:从生物分子到超分子药物化学
Biomedicines. 2022 Apr 12;10(4):885. doi: 10.3390/biomedicines10040885.
5
Gene Therapy for Rhodopsin-associated Autosomal Dominant Retinitis Pigmentosa.视紫红质相关常染色体显性遗传性视网膜色素变性的基因治疗
Int Ophthalmol Clin. 2021 Oct 1;61(4):79-96. doi: 10.1097/IIO.0000000000000383.
一种用于评估光遗传学工具对视功能恢复效果的稳健光感受器运动检测法。
Invest Ophthalmol Vis Sci. 2018 Mar 1;59(3):1288-1294. doi: 10.1167/iovs.17-23278.
4
Optogenetic Approaches to Restoring Vision.恢复视力的光遗传学方法。
Annu Rev Vis Sci. 2015 Nov 24;1:185-210. doi: 10.1146/annurev-vision-082114-035532.
5
Targeted Expression of Channelrhodopsin-2 to the Axon Initial Segment Alters the Temporal Firing Properties of Retinal Ganglion Cells.将视紫红质通道蛋白-2靶向表达于轴突起始段会改变视网膜神经节细胞的放电时间特性。
PLoS One. 2015 Nov 4;10(11):e0142052. doi: 10.1371/journal.pone.0142052. eCollection 2015.
6
Restoration of Vision with Ectopic Expression of Human Rod Opsin.通过人视杆视蛋白的异位表达恢复视力
Curr Biol. 2015 Aug 17;25(16):2111-22. doi: 10.1016/j.cub.2015.07.029. Epub 2015 Jul 30.
7
Optogenetic Vision Restoration Using Rhodopsin for Enhanced Sensitivity.使用视紫红质增强敏感性的光遗传学视觉恢复
Mol Ther. 2015 Oct;23(10):1562-71. doi: 10.1038/mt.2015.121. Epub 2015 Jul 3.
8
ChR2 mutants at L132 and T159 with improved operational light sensitivity for vision restoration.用于视力恢复的、在L132和T159位点具有改善的光操作敏感性的ChR2突变体。
PLoS One. 2014 Jun 5;9(6):e98924. doi: 10.1371/journal.pone.0098924. eCollection 2014.
9
rAAV-mediated subcellular targeting of optogenetic tools in retinal ganglion cells in vivo.体内活体视网膜神经节细胞中光遗传工具的 rAAV 介导的亚细胞靶向。
PLoS One. 2013 Jun 14;8(6):e66332. doi: 10.1371/journal.pone.0066332. Print 2013.
10
Undersized dendritic arborizations in retinal ganglion cells of the rd1 mutant mouse: a paradigm of early onset photoreceptor degeneration.rd1 突变小鼠视网膜神经节细胞中小尺寸树突分支:早期光感受器变性范例。
J Comp Neurol. 2012 May 1;520(7):1406-23. doi: 10.1002/cne.22802.