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麻木缺陷损害小鼠的视网膜结构和视觉功能。

Numb deficiency impairs retinal structure and visual function in mice.

机构信息

Eye Center, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, Hubei, China.

Eye Center, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, Hubei, China; Department of Ophthalmology, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, 519000, Guangdong Province, China.

出版信息

Exp Eye Res. 2022 Jun;219:109066. doi: 10.1016/j.exer.2022.109066. Epub 2022 Apr 15.

DOI:10.1016/j.exer.2022.109066
PMID:35430256
Abstract

PURPOSE

Numb is expressed in the progenitor and mature neurons throughout the development progress of the retina. We attempted to investigate the role of Numb in the retina and visual system, and the effects of Numb deficiency on retinal structure and visual function.

METHODS

Conditional Numb/Nbl double-knockout mice were generated to observe the retinal damage in Numb deficiency mice. HE staining and immunofluorescence stain were used to observe the structural and molecular changes. The visual function was assessed by electroretinogram (ERG) and optomotor response (OMR). RNA-Seq and RT-PCR were used to detect the differential expression of genes and the related signaling pathways.

RESULTS

Inactivation of Numb/Nbl induces eye apoptosis and retinal neurons impairment observed by HE staining and immunofluorescence stain. The impaired retinal structure and visual function were assessed by ERG and OMR. RNA-seq analysis indicated loss of photoreceptors, synapses and phototransduction related molecules. Immunofluorescence stain of molecular markers recoverin, arrestin, rhodopsin showed disrupted structural integrity of photoreceptors. Additional bipolar cells and synapses related molecular markers indicate synaptic connections were damaged in Numb deficiency mice.

CONCLUSIONS

Inactivation of Numb/Nbl induces eye apoptosis and retinal neurons impairment. Ablation of Numb in retina significantly impaired visual function. The impaired visual function in Numb deficiency mice is related to the damage of photoreceptors, ion/cation channel activity, synapse formation and phototransduction.

摘要

目的

Numb 在视网膜的发育过程中表达于祖细胞和成熟神经元。我们试图研究 Numb 在视网膜和视觉系统中的作用,以及 Numb 缺失对视网膜结构和视觉功能的影响。

方法

通过生成条件性 Numb/Nbl 双敲除小鼠来观察 Numb 缺失小鼠的视网膜损伤。通过 HE 染色和免疫荧光染色观察结构和分子变化。通过视网膜电图(ERG)和光运动反应(OMR)评估视觉功能。通过 RNA-Seq 和 RT-PCR 检测基因差异表达和相关信号通路。

结果

Numb/Nbl 的失活诱导眼睛凋亡和视网膜神经元损伤,这可通过 HE 染色和免疫荧光染色观察到。ERG 和 OMR 评估受损的视网膜结构和视觉功能。RNA-seq 分析表明光感受器、突触和光转导相关分子缺失。分子标志物 recoverin、arrestin、rhodopsin 的免疫荧光染色显示光感受器结构完整性受损。额外的双极细胞和突触相关分子标志物表明 Numb 缺失小鼠的突触连接受损。

结论

Numb/Nbl 的失活诱导眼睛凋亡和视网膜神经元损伤。视网膜中 Numb 的缺失显著损害了视觉功能。Numb 缺失小鼠的视觉功能障碍与光感受器、离子/阳离子通道活性、突触形成和光转导的损伤有关。

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