• 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

Rho 激酶抑制增强 Fuchs 角膜内皮细胞迁移：一种新型的离体单纯 Descemet 膜撕除模型。

Enhanced Migration of Fuchs Corneal Endothelial Cells by Rho Kinase Inhibition: A Novel Ex Vivo Descemet's Stripping Only Model.

机构信息

Schepens Eye Research Institute of Mass Eye and Ear, Department of Ophthalmology, Harvard Medical School, 20 Staniford Street, Boston, MA 02114, USA.

Faculty of Arts and Sciences, Harvard College, Boston, MA 02138, USA.

出版信息

Cells. 2024 Jul 19;13(14):1218. doi: 10.3390/cells13141218.

DOI:10.3390/cells13141218
PMID:39056800
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11274477/
Abstract

Descemet's Stripping Only (DSO) is a surgical technique that utilizes the peripheral corneal endothelial cell (CEnC) migration for wound closure. Ripasudil, a Rho-associated protein kinase (ROCK) inhibitor, has shown potential in DSO treatment; however, its mechanism in promoting CEnC migration remains unclear. We observed that ripasudil-treated immortalized normal and Fuchs endothelial corneal dystrophy (FECD) cells exhibited significantly enhanced migration and wound healing, particularly effective in FECD cells. Ripasudil upregulated mRNA expression of Snail Family Transcriptional Repressor () and Vimentin () while decreasing Cadherin (), indicating endothelial-to-mesenchymal transition (EMT) activation. Ripasudil activated Rac1, driving the actin-related protein complex (ARPC2) to the leading edge, facilitating enhanced migration. Ex vivo studies on cadaveric and FECD Descemet's membrane (DM) showed increased migration and proliferation of CEnCs after ripasudil treatment. An ex vivo DSO model demonstrated enhanced migration from the DM to the stroma with ripasudil. Coating small incision lenticule extraction (SMILE) tissues with an FNC coating mix and treating the cells in conjunction with ripasudil further improved migration and resulted in a monolayer formation, as detected by the ZO-1 junctional marker, thereby leading to the reduction in EMT. In conclusion, ripasudil effectively enhanced cellular migration, particularly in a novel ex vivo DSO model, when the stromal microenvironment was modulated. This suggests ripasudil as a promising adjuvant for DSO treatment, highlighting its potential clinical significance.

摘要

Descemet's Stripping Only (DSO) 是一种利用周边角膜内皮细胞 (CEnC) 迁移进行伤口闭合的手术技术。Ripasudil 是一种 Rho 相关蛋白激酶 (ROCK) 抑制剂，已显示出在 DSO 治疗中的潜力；然而，其促进 CEnC 迁移的机制尚不清楚。我们观察到，ripasudil 处理的永生化正常和 Fuchs 内皮角膜营养不良 (FECD) 细胞表现出明显增强的迁移和伤口愈合能力，特别是在 FECD 细胞中效果显著。Ripasudil 上调了 Snail Family Transcriptional Repressor () 和 Vimentin () 的 mRNA 表达，同时降低了 Cadherin ()，表明内皮细胞向间充质转化 (EMT) 激活。Ripasudil 激活了 Rac1，驱动肌动蛋白相关蛋白复合物 (ARPC2) 到达前缘，促进了增强的迁移。对尸体和 FECD Descemet 膜 (DM) 的离体研究表明，ripasudil 处理后 CEnC 的迁移和增殖增加。离体 DSO 模型显示，ripasudil 可促进 DM 向基质迁移。用 FNC 涂层混合物涂覆小切口透镜提取 (SMILE) 组织并结合 ripasudil 处理细胞进一步改善了迁移，并通过 ZO-1 连接标记物检测到单层形成，从而导致 EMT 减少。总之，当调节基质微环境时，ripasudil 可有效增强细胞迁移，特别是在新型离体 DSO 模型中。这表明 ripasudil 作为 DSO 治疗的一种有前途的辅助手段，突出了其潜在的临床意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6283/11274477/8ccecc683d2f/cells-13-01218-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6283/11274477/f17fd5e02a2f/cells-13-01218-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6283/11274477/d2fc7793b55b/cells-13-01218-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6283/11274477/a49fa9b33746/cells-13-01218-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6283/11274477/1a8c715b1eec/cells-13-01218-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6283/11274477/ed0c8c359bca/cells-13-01218-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6283/11274477/21c0701381e2/cells-13-01218-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6283/11274477/ae124b8f79cf/cells-13-01218-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6283/11274477/262b999d71f5/cells-13-01218-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6283/11274477/8ccecc683d2f/cells-13-01218-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6283/11274477/f17fd5e02a2f/cells-13-01218-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6283/11274477/d2fc7793b55b/cells-13-01218-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6283/11274477/a49fa9b33746/cells-13-01218-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6283/11274477/1a8c715b1eec/cells-13-01218-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6283/11274477/ed0c8c359bca/cells-13-01218-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6283/11274477/21c0701381e2/cells-13-01218-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6283/11274477/ae124b8f79cf/cells-13-01218-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6283/11274477/262b999d71f5/cells-13-01218-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6283/11274477/8ccecc683d2f/cells-13-01218-g009.jpg

相似文献

1
Enhanced Migration of Fuchs Corneal Endothelial Cells by Rho Kinase Inhibition: A Novel Ex Vivo Descemet's Stripping Only Model.Rho 激酶抑制增强 Fuchs 角膜内皮细胞迁移：一种新型的离体单纯 Descemet 膜撕除模型。
Cells. 2024 Jul 19;13(14):1218. doi: 10.3390/cells13141218.
2
Potential Functional Restoration of Corneal Endothelial Cells in Fuchs Endothelial Corneal Dystrophy by ROCK Inhibitor (Ripasudil).ROCK抑制剂（瑞帕舒迪）对Fuchs内皮角膜营养不良中角膜内皮细胞的潜在功能恢复作用
Am J Ophthalmol. 2021 Apr;224:185-199. doi: 10.1016/j.ajo.2020.12.006. Epub 2020 Dec 11.
3
Descemet Stripping Only Supplemented With Topical Ripasudil for Fuchs Endothelial Dystrophy 12-Month Outcomes of the Sydney Eye Hospital Study.仅行 Descemet 膜撕除术联合局部应用 ripasudil 治疗 Fuchs 内皮营养不良：悉尼眼科医院研究的 12 个月结果。
Cornea. 2021 Mar 1;40(3):320-326. doi: 10.1097/ICO.0000000000002437.
4
Use of Topical Rho Kinase Inhibitors in the Treatment of Fuchs Dystrophy After Descemet Stripping Only.仅行后弹力层剥除术后，局部使用 Rho 激酶抑制剂治疗 Fuchs 角膜内皮营养不良
Cornea. 2019 May;38(5):529-534. doi: 10.1097/ICO.0000000000001883.
5
Descemet Endothelial Thickness Comparison Trial II (DETECT II): multicentre, outcome assessor-masked, placebo-controlled trial comparing Descemet membrane endothelial keratoplasty (DMEK) to Descemet stripping only (DSO) with adjunctive ripasudil for Fuchs dystrophy.Descemet 内皮细胞厚度比较试验 II（DETECT II）：多中心、结局评估者盲法、安慰剂对照试验，比较用于 Fuchs 营养不良的 Descemet 膜内皮角膜移植术（DMEK）与单纯 Descemet 膜撕除术（DSO）联合 ripasudil 的疗效。
BMJ Open Ophthalmol. 2024 Oct 1;9(1):e001725. doi: 10.1136/bmjophth-2024-001725.
6
A Human Corneal Organ Culture Model of Descemet's Stripping Only with Accelerated Healing Stimulated by Engineered Fibroblast Growth Factor 1.一种仅通过工程化成纤维细胞生长因子 1 刺激加速愈合的人角膜去表皮化器官培养模型。
J Vis Exp. 2022 Jul 22(185). doi: 10.3791/63482.
7
Descemet stripping only and ripasudil for the treatment of traumatic Descemet's membrane ruptures.单纯后弹力层剥除联合瑞巴派特治疗外伤性后弹力层破裂
Eur J Ophthalmol. 2023 Jul;33(4):NP13-NP18. doi: 10.1177/11206721221095598. Epub 2022 Apr 18.
8
Descemet's stripping without endothelial keratoplasty.撕除 Descemet 膜，不进行内皮角膜移植术。
Curr Opin Ophthalmol. 2019 Jul;30(4):275-285. doi: 10.1097/ICU.0000000000000579.
9
In vivo confocal microscopy findings after Descemet stripping only with and without topical ripasudil supplementation in Fuchs endothelial dystrophy.Fuchs 内皮营养不良行单纯 Descemet 膜撕除术与联合 ripasudil 滴眼后共焦显微镜观察。
Can J Ophthalmol. 2024 Dec;59(6):e682-e690. doi: 10.1016/j.jcjo.2024.02.016. Epub 2024 Mar 16.
10
Rho-Associated Kinase Inhibitor Eye Drop (Ripasudil) Transiently Alters the Morphology of Corneal Endothelial Cells.Rho相关激酶抑制剂滴眼液（ripasudil）可短暂改变角膜内皮细胞形态。
Invest Ophthalmol Vis Sci. 2015 Nov;56(12):7560-7. doi: 10.1167/iovs.15-17887.

引用本文的文献

1
A Comprehensive Review of the Role of Rho-Kinase Inhibitors in Corneal Diseases.Rho激酶抑制剂在角膜疾病中作用的综合综述
Life (Basel). 2025 Aug 13;15(8):1283. doi: 10.3390/life15081283.
2
Therapeutic Potential of Rho Kinase Inhibitors in Corneal Disease: A Systematic Review of Preclinical and Clinical Studies.Rho激酶抑制剂在角膜疾病中的治疗潜力：临床前和临床研究的系统评价
Biomedicines. 2025 Jun 30;13(7):1602. doi: 10.3390/biomedicines13071602.
3
Preclinical Models for Studying Fuchs Endothelial Corneal Dystrophy.用于研究富克斯角膜内皮营养不良的临床前模型

本文引用的文献

1
Transcription factor 4 promotes increased corneal endothelial cellular migration by altering microtubules in Fuchs endothelial corneal dystrophy.转录因子 4 通过改变 Fuchs 内皮角膜营养不良中的微管促进角膜内皮细胞迁移增加。
Sci Rep. 2024 May 4;14(1):10276. doi: 10.1038/s41598-024-61170-8.
2
Early and late-onset cell migration from peripheral corneal endothelium.周边角膜内皮细胞的早期和晚期细胞迁移。
PLoS One. 2023 May 10;18(5):e0285609. doi: 10.1371/journal.pone.0285609. eCollection 2023.
3
Increased Corneal Endothelial Cell Migration in Fuchs Endothelial Corneal Dystrophy: A Live Cell Imaging Study.
Cells. 2025 Mar 28;14(7):505. doi: 10.3390/cells14070505.
4
Descemet Stripping Only for Symptomatic Fuchs Endothelial Dystrophy-A Retrospective Case Series Comparing ROCK-I vs. Hypertonic Sodium Chloride for Post-Surgical Adjuvant Therapy.仅行后弹力层剥除术治疗症状性Fuchs内皮营养不良——一项比较ROCK-I与高渗氯化钠用于术后辅助治疗的回顾性病例系列研究
J Clin Med. 2025 Feb 24;14(5):1512. doi: 10.3390/jcm14051512.
5
RHO-Associated Coiled-Coil-Containing Protein Kinase Inhibitors Significantly Modulate the Epithelial-Mesenchymal Transition Induced by TGF-β2 in the 2-D and 3-D Cultures of Human Corneal Stroma Fibroblasts.RHO相关卷曲螺旋蛋白激酶抑制剂在人角膜基质成纤维细胞的二维和三维培养中显著调节由转化生长因子-β2诱导的上皮-间质转化。
Biomedicines. 2024 Dec 6;12(12):2784. doi: 10.3390/biomedicines12122784.
富克斯内皮性角膜营养不良中角膜内皮细胞迁移增加：一项活细胞成像研究。
Ophthalmol Sci. 2021 Mar 9;1(1):100006. doi: 10.1016/j.xops.2021.100006. eCollection 2021 Mar.
4
Impact of Repeat Number on Resolution of Corneal Edema after Descemet's Stripping Only in Fuchs Dystrophy: A Pilot Study.仅行Descemet膜剥除术治疗Fuchs角膜内皮营养不良时重复次数对角膜水肿消退的影响：一项初步研究
Vision (Basel). 2021 Oct 9;5(4):47. doi: 10.3390/vision5040047.
5
Cytoskeletal Dynamics in Epithelial-Mesenchymal Transition: Insights into Therapeutic Targets for Cancer Metastasis.上皮-间质转化中的细胞骨架动力学：对癌症转移治疗靶点的见解
Cancers (Basel). 2021 Apr 14;13(8):1882. doi: 10.3390/cancers13081882.
6
Pilot Study of Corneal Clearance With the Use of a Rho-Kinase Inhibitor After Descemetorhexis Without Endothelial Keratoplasty for Fuchs Endothelial Corneal Dystrophy.Rho 激酶抑制剂在非穿透性角膜内皮移植术后用于 Fuchs 内皮角膜营养不良的撕囊后角膜水肿消退的初步研究。
Cornea. 2021 Jul 1;40(7):899-902. doi: 10.1097/ICO.0000000000002691.
7
Cell cycle re-entry and arrest in G2/M phase induces senescence and fibrosis in Fuchs Endothelial Corneal Dystrophy.细胞周期重新进入并停滞于G2/M期会诱导富克斯角膜内皮营养不良中的细胞衰老和纤维化。
Free Radic Biol Med. 2021 Feb 20;164:34-43. doi: 10.1016/j.freeradbiomed.2020.12.445. Epub 2021 Jan 6.
8
Potential Functional Restoration of Corneal Endothelial Cells in Fuchs Endothelial Corneal Dystrophy by ROCK Inhibitor (Ripasudil).ROCK抑制剂（瑞帕舒迪）对Fuchs内皮角膜营养不良中角膜内皮细胞的潜在功能恢复作用
Am J Ophthalmol. 2021 Apr;224:185-199. doi: 10.1016/j.ajo.2020.12.006. Epub 2020 Dec 11.
9
Corneal endothelial dysfunction: Evolving understanding and treatment options.角膜内皮功能障碍：不断发展的认识和治疗选择。
Prog Retin Eye Res. 2021 May;82:100904. doi: 10.1016/j.preteyeres.2020.100904. Epub 2020 Sep 22.
10
Human corneal endothelial cells from older donors can be cultured and passaged on cell-derived extracellular matrix.人眼角膜内皮细胞可从老年供体中培养和传代于细胞衍生的细胞外基质上。
Acta Ophthalmol. 2021 Jun;99(4):e512-e522. doi: 10.1111/aos.14614. Epub 2020 Sep 10.