A systematic comparison of optogenetic approaches to visual restoration.
A systematic comparison of optogenetic approaches to visual restoration.
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DOI：
10.1016/j.omtm.2022.03.003
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发表时间：
2022-06-09
期刊：
影响因子：
--
通讯作者：
Hankins MW
中科院分区：
文献类型：
--
作者：
Gilhooley MJ;Lindner M;Palumaa T;Hughes S;Peirson SN;Hankins MW
在遗传性视网膜变性（IRD）期间，由于感光细胞死亡而丧失视力;然而，一系列光遗传学工具已被证明可以在动物模型中恢复光反应。恢复的反应特征在工具和它们被递送到的神经元细胞群体之间变化：这些之间的相互作用是复杂的，但是靶向上游神经元（例如视网膜双极细胞）可以通过保留视网膜内信号处理来提供功能益处。在这项研究中，我们的目的是比较两种光遗传学工具：哺乳动物黑视蛋白（hOPN 4）和微生物红移通道视紫红质（ReaChR）在退化视网膜中的两个存活细胞亚群中表达。利用Cre/lox系统的玻璃体内腺相关病毒载体和小鼠模型将表达限制在由双极细胞或视网膜神经节细胞主导的群体中，并与使用鸡β肌动蛋白（CBA）启动子的非靶向递送进行比较。总之，我们发现与非靶向或视网膜神经节细胞靶向hOPN 4相比，双极靶向光遗传学工具产生更快的动力学和更平坦的强度-响应关系。因此，哺乳动物和微生物来源的光遗传学工具在靶向双极细胞时显示出优势。这证明了双极细胞靶向光遗传学在IRD视力恢复中的优势。因此，我们开发了一种双极细胞特异性基因传递系统，采用压缩的启动子与临床翻译的潜力。光遗传学代表了遗传性视网膜变性的一种有希望的潜在治疗选择;然而，哪种光遗传学工具或靶细胞群将是最有效的尚不清楚。这项研究首次在视网膜退化小鼠模型中直接比较了潜在的工具和递送途径。
During inherited retinal degenerations (IRDs), vision is lost due to photoreceptor cell death; however, a range of optogenetic tools have been shown to restore light responses in animal models. Restored response characteristics vary between tools and the neuronal cell population to which they are delivered: the interplay between these is complex, but targeting upstream neurons (such as retinal bipolar cells) may provide functional benefit by retaining intraretinal signal processing. In this study, our aim was to compare two optogenetic tools: mammalian melanopsin (hOPN4) and microbial red-shifted channelrhodopsin (ReaChR) expressed within two subpopulations of surviving cells in a degenerate retina. Intravitreal adeno-associated viral vectors and mouse models utilising the Cre/lox system restricted expression to populations dominated by bipolar cells or retinal ganglion cells and was compared with non-targeted delivery using the chicken beta actin (CBA) promoter. In summary, we found bipolar-targeted optogenetic tools produced faster kinetics and flatter intensity-response relationships compared with non-targeted or retinal-ganglion-cell-targeted hOPN4. Hence, optogenetic tools of both mammalian and microbial origins show advantages when targeted to bipolar cells. This demonstrates the advantage of bipolar-cell-targeted optogenetics for vision restoration in IRDs. We therefore developed a bipolar-cell-specific gene delivery system employing a compressed promoter with the potential for clinical translation. Optogenetics represents a promising potential therapeutic option in the inherited retinal degenerations; which optogenetic tool or target cell population will be most effective is, however, unknown. This study, for the first time, directly compares potential tools and delivery routes in a retinal degenerate mouse model.
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影响因子：
2.9
作者：
Blasic, Joseph R., Jr.;Matos-Cruz, Vanessa;Robinson, Phyllis R.
通讯作者：
Robinson, Phyllis R.
影响因子：
3.3
作者：
Ivanova, E.;Hwang, G. -S.;Pan, Z. -H.
通讯作者：
Pan, Z. -H.
影响因子：
11.1
作者：
Cronin T;Vandenberghe LH;Hantz P;Juttner J;Reimann A;Kacsó AE;Huckfeldt RM;Busskamp V;Kohler H;Lagali PS;Roska B;Bennett J
通讯作者：
Bennett J
影响因子：
8
作者：
Hughes, Steven;Jagannath, Aarti;Hankins, Mark W.
通讯作者：
Hankins, Mark W.
DOI：
10.1038/mtm.2013.5
发表时间：
2014-01-08
期刊：
Molecular therapy. Methods & clinical development
影响因子：
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作者：
通讯作者：
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