• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

小鼠中RORα基因缺失通过视杆双极细胞变性损害视觉功能。

Genetic Loss of RORα Impairs Visual Function With Rod Bipolar Cell Degeneration In Mice.

作者信息

Bora Kiran, Liu Chi-Hsiu, Kushwah Neetu, Maurya Meenakshi, Pavlovich Madeline C, Solt Laura A, Sun Ye, Fu Zhongjie, Akula James D, Chen Jing

机构信息

Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States.

Department of Immunology and Microbiology, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technology, Jupiter, Florida, United States.

出版信息

Invest Ophthalmol Vis Sci. 2025 Aug 1;66(11):20. doi: 10.1167/iovs.66.11.20.

DOI:10.1167/iovs.66.11.20
PMID:40778701
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12347186/
Abstract

PURPOSE

Retinoic acid receptor-related orphan receptor alpha (RORα) is a ligand-dependent nuclear receptor involved in eye development and diseases. Genetic variations of RORα have been linked with the development of age-related macular degeneration, yet whether RORα regulates visual function is unknown. In this study we investigated the role of RORα in regulating visual function in mice with genetic deficiency of RORα.

METHODS

RORα deficient staggerer (Rorasg/sg) and age-matched wild type control mice were assessed for visual function using electroretinography (ERG). Retinal localization of RORα and rod bipolar cell morphology were assessed using immunohistochemistry. Retinal thickness was measured as well as presence of retinal gliosis, and expression of genes in visual transduction.

RESULTS

RORα is expressed in photoreceptors, retinal ganglion cells, and bipolar cells. Genetic deletion of RORα in Rorasg/sg mice markedly impaired visual function measured by ERG, with substantial attenuation of b-wave amplitude compared with wild type controls, reflective of bipolar cell dysfunction. Rorasg/sg eyes showed significant degeneration of rod bipolar cells and retinal gliosis, both of which progressed upon aging. Moreover, loss of ROR⍺ also resulted in significant retinal thinning, including both outer and inner nuclear layers. Expression of genes involved in phototransduction and rod bipolar cell depolarization was upregulated in Rorasg/sg retinas, suggestive of potential compensatory remodeling of visual signaling.

CONCLUSIONS

Our findings demonstrate that RORα is indispensable for the structural and functional maintenance of rod bipolar cells and could pose as a potential therapeutic target for mitigating bipolar cell deficits in retinal degenerative diseases.

摘要

目的

维甲酸受体相关孤儿受体α（RORα）是一种参与眼睛发育和疾病的配体依赖性核受体。RORα的基因变异与年龄相关性黄斑变性的发生有关，但RORα是否调节视觉功能尚不清楚。在本研究中，我们研究了RORα基因缺陷小鼠中RORα在调节视觉功能中的作用。

方法

使用视网膜电图（ERG）评估RORα缺陷的蹒跚小鼠（Rorasg/sg）和年龄匹配的野生型对照小鼠的视觉功能。使用免疫组织化学评估RORα的视网膜定位和视杆双极细胞形态。测量视网膜厚度以及视网膜胶质增生的存在情况，以及视觉转导中基因的表达。

结果

RORα在光感受器、视网膜神经节细胞和双极细胞中表达。Rorasg/sg小鼠中RORα的基因缺失显著损害了通过ERG测量的视觉功能，与野生型对照相比，b波振幅大幅衰减，这反映了双极细胞功能障碍。Rorasg/sg小鼠的眼睛显示视杆双极细胞明显退化和视网膜胶质增生，两者都随着年龄的增长而进展。此外，RORα的缺失还导致视网膜显著变薄，包括外核层和内核层。参与光转导和视杆双极细胞去极化的基因在Rorasg/sg视网膜中的表达上调，提示视觉信号可能存在代偿性重塑。

结论

我们的研究结果表明，RORα对于视杆双极细胞的结构和功能维持是不可或缺的，并且可能成为减轻视网膜退行性疾病中双极细胞缺陷的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdc8/12347186/d937187a61c7/iovs-66-11-20-f006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdc8/12347186/65586680d89b/iovs-66-11-20-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdc8/12347186/c4f3b910aa9e/iovs-66-11-20-f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdc8/12347186/6e3d10d7fa21/iovs-66-11-20-f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdc8/12347186/166cb1d66ffd/iovs-66-11-20-f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdc8/12347186/bdeaea31d094/iovs-66-11-20-f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdc8/12347186/d937187a61c7/iovs-66-11-20-f006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdc8/12347186/65586680d89b/iovs-66-11-20-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdc8/12347186/c4f3b910aa9e/iovs-66-11-20-f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdc8/12347186/6e3d10d7fa21/iovs-66-11-20-f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdc8/12347186/166cb1d66ffd/iovs-66-11-20-f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdc8/12347186/bdeaea31d094/iovs-66-11-20-f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdc8/12347186/d937187a61c7/iovs-66-11-20-f006.jpg

相似文献

1
Genetic Loss of RORα Impairs Visual Function With Rod Bipolar Cell Degeneration In Mice.小鼠中RORα基因缺失通过视杆双极细胞变性损害视觉功能。
Invest Ophthalmol Vis Sci. 2025 Aug 1;66(11):20. doi: 10.1167/iovs.66.11.20.
2
A new mouse model for PRPH2 pattern dystrophy exhibits functional compensation prior and subsequent to retinal degeneration.一种新的 PRPH2 模式营养不良的小鼠模型在视网膜变性前后表现出功能代偿。
Hum Mol Genet. 2024 Nov 5;33(21):1916-1928. doi: 10.1093/hmg/ddae128.
3
In vivo efficacy of NRL knockdown with cell-penetrating siRNA in retinal degeneration.细胞穿透性小干扰RNA敲低NRL在视网膜变性中的体内疗效
Sci Rep. 2025 Jul 26;15(1):27176. doi: 10.1038/s41598-025-07299-6.
4
Photoreceptor degeneration induces homeostatic rewiring of rod bipolar cells.光感受器退化会诱导视杆双极细胞进行稳态重布线。
Curr Biol. 2025 Jun 25. doi: 10.1016/j.cub.2025.05.057.
5
A longitudinal study of the 5xFAD mouse retina delineates Amyloid beta (Aβ)-mediated retinal pathology from age-related changes.一项对5xFAD小鼠视网膜的纵向研究区分了淀粉样β蛋白（Aβ）介导的视网膜病变与年龄相关变化。
Alzheimers Res Ther. 2025 Jun 19;17(1):136. doi: 10.1186/s13195-025-01784-w.
6
Protein kinase G inhibition preserves photoreceptor viability and function in a new mouse model for autosomal dominant retinitis pigmentosa.在一种新的常染色体显性视网膜色素变性小鼠模型中，蛋白激酶G抑制可维持光感受器的活力和功能。
Cell Death Dis. 2025 Jul 30;16(1):575. doi: 10.1038/s41419-025-07901-9.
7
Transcriptomic Analysis Reveals That Excessive Thyroid Hormone Signaling Impairs Phototransduction and Mitochondrial Bioenergetics and Induces Cellular Stress in Mouse Cone Photoreceptors.转录组分析揭示，甲状腺激素信号过度激活会损害光感受器的光转导和线粒体生物能，并诱导细胞应激。
Int J Mol Sci. 2024 Jul 6;25(13):7435. doi: 10.3390/ijms25137435.
8
Scavenging acrolein with 2-HDP preserves neurovascular integrity in a rat model of diabetic retinal disease.用2-羟基二氢吡啶清除丙烯醛可在糖尿病视网膜病变大鼠模型中维持神经血管完整性。
Diabetologia. 2025 Aug 15. doi: 10.1007/s00125-025-06515-2.
9
Epigenetic Modifiers to Treat Retinal Degenerative Diseases.用于治疗视网膜退行性疾病的表观遗传修饰剂
Cells. 2025 Jun 23;14(13):961. doi: 10.3390/cells14130961.
10
Interruption of the visual cycle in a novel animal model induces progressive vision loss resembling Stargardts Disease.在一种新型动物模型中视觉循环的中断会引发类似于斯塔加特病的进行性视力丧失。
Sci Rep. 2024 Dec 28;14(1):30880. doi: 10.1038/s41598-024-81869-y.

本文引用的文献

1
The Circadian Clock of Müller Glia Is Necessary for Retinal Homeostasis and Neuronal Survival.Müller 胶质细胞的生物钟对于视网膜内稳态和神经元存活是必需的。
Am J Pathol. 2024 Nov;194(11):2179-2193. doi: 10.1016/j.ajpath.2024.07.017. Epub 2024 Aug 13.
2
The Effects of Aging on Rod Bipolar Cell Ribbon Synapses.衰老对视杆细胞双极细胞带状突触的影响。
Cells. 2023 Sep 29;12(19):2385. doi: 10.3390/cells12192385.
3
Neuroprotective role for RORA in Parkinson's disease revealed by analysis of post-mortem brain and a dopaminergic cell line.
通过对尸检大脑和多巴胺能细胞系的分析揭示RORA在帕金森病中的神经保护作用。
NPJ Parkinsons Dis. 2023 Jul 27;9(1):119. doi: 10.1038/s41531-023-00563-4.
4
Genetic deficiency and pharmacological modulation of RORα regulate laser-induced choroidal neovascularization.遗传缺陷和 RORα 的药理学调节可调控激光诱导的脉络膜新生血管。
Aging (Albany NY). 2023 Jan 10;15(1):37-52. doi: 10.18632/aging.204480.
5
Congenital Stationary Night Blindness: Clinical and Genetic Features.先天性静止性夜盲症：临床和遗传特征。
Int J Mol Sci. 2022 Nov 29;23(23):14965. doi: 10.3390/ijms232314965.
6
Bipolar cell targeted optogenetic gene therapy restores parallel retinal signaling and high-level vision in the degenerated retina.双极细胞靶向光遗传学基因治疗恢复了变性视网膜中的平行视网膜信号和高级视觉。
Commun Biol. 2022 Oct 20;5(1):1116. doi: 10.1038/s42003-022-04016-1.
7
Cellular and molecular alterations in neurons and glial cells in inherited retinal degeneration.遗传性视网膜变性中神经元和神经胶质细胞的细胞及分子改变。
Front Neuroanat. 2022 Sep 26;16:984052. doi: 10.3389/fnana.2022.984052. eCollection 2022.
8
Structural and functional retinal alterations in patients with paranoid schizophrenia.偏执型精神分裂症患者的视网膜结构和功能改变。
Transl Psychiatry. 2022 Sep 23;12(1):402. doi: 10.1038/s41398-022-02167-7.
9
Retinal inner nuclear layer thinning is decreased and associates with the clinical outcome in ocrelizumab-treated primary progressive multiple sclerosis.奥瑞珠单抗治疗原发性进行性多发性硬化症患者视网膜内核层变薄减少，并与临床结局相关。
J Neurol. 2022 Oct;269(10):5436-5442. doi: 10.1007/s00415-022-11183-y. Epub 2022 Jun 1.
10
Photoreceptor Layer Thinning Is an Early Biomarker for Age-Related Macular Degeneration: Epidemiologic and Genetic Evidence from UK Biobank OCT Data.光感受器层变薄是年龄相关性黄斑变性的早期生物标志物：来自英国生物银行OCT数据的流行病学和遗传学证据。
Ophthalmology. 2022 Jun;129(6):694-707. doi: 10.1016/j.ophtha.2022.02.001. Epub 2022 Feb 8.