• 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 激酶抑制剂奈立定对远端流出道的剂量依赖性作用。

Dose-dependent effects of netarsudil, a Rho-kinase inhibitor, on the distal outflow tract.

机构信息

Department of Ophthalmology, University of Würzburg, Josef-Schneider-Straße 11, 97080, Würzburg, Germany.

Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

出版信息

Graefes Arch Clin Exp Ophthalmol. 2020 Jun;258(6):1211-1216. doi: 10.1007/s00417-020-04691-y. Epub 2020 May 5.

DOI:10.1007/s00417-020-04691-y
PMID:32372330
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7237522/
Abstract

PURPOSE

To characterize the effects of netarsudil on the aqueous humor outflow tract distal to the trabecular meshwork (TM). We hypothesized that netarsudil increases outflow facility in eyes with and without circumferential ab interno trabeculectomy (AIT) that removes the TM.

METHODS

Sixty-four porcine anterior segment cultures were randomly assigned to groups with (n = 32) and without circumferential AIT (n = 32). Cultures were exposed to 0.1, 1, and 10 μM netarsudil (N = 8 eyes per concentration). For each concentration, IOP and vessel diameters were compared with their respective pretreatment baselines. Outflow tract vessel diameters were assessed by spectral-domain optical coherence tomography (SDOCT) and rendered in 4D (XYZ time series).

RESULTS

Netarsudil at 1 μM reduced IOP both in eyes with TM (- 0.60 ± 0.24 mmHg, p = 0.01) and in eyes without TM (- 1.79 ± 0.42 mmHg, p < 0.01). At this concentration, vessels of the distal outflow tract dilated by 72%. However, at 0.1 μM netarsudil elevated IOP in eyes with TM (1.59 ± 0.36 mmHg, p < 0.001) as well as in eyes without TM (0.23 ± 0.32 mmHg, p < 0.001). Vessels of the distal outflow tract constricted by 31%. Similarly, netarsudil at a concentration of 10 μM elevated IOP both in eyes with TM (1.91 ± 0.193, p < 0.001) and in eyes without TM (3.65 ± 0.86 mmHg, p < 0.001). At this concentration, outflow tract vessels constricted by 27%.

CONCLUSION

In the porcine anterior segment culture, the dose-dependent IOP changes caused by netarsudil matched the diameter changes of distal outflow tract vessels. Hyper- and hypotensive properties of netarsudil persisted after TM removal.

摘要

目的

描述奈塔舒利对小梁网后房水流出道的作用。我们假设奈塔舒利能增加有和没有环内小梁切除术(AIT)的眼睛的房水流出率,因为 AIT 去除了小梁网。

方法

64 个猪眼前节培养物被随机分为有(n=32)和没有(n=32)环内 AIT 的两组。培养物暴露于 0.1、1 和 10 μM 的奈塔舒利(每种浓度 8 只眼)。对于每种浓度,IOP 和血管直径与各自的预处理基线进行比较。房水流出道血管直径通过光谱域光学相干断层扫描(SDOCT)评估,并在 4D(XYZ 时间序列)中呈现。

结果

1 μM 的奈塔舒利降低了有小梁网的眼睛(-0.60±0.24mmHg,p=0.01)和没有小梁网的眼睛(-1.79±0.42mmHg,p<0.01)的 IOP。在这个浓度下,远端流出道的血管扩张了 72%。然而,在 0.1 μM 的奈塔舒利时,有小梁网的眼睛的 IOP 升高(1.59±0.36mmHg,p<0.001)和没有小梁网的眼睛的 IOP 升高(0.23±0.32mmHg,p<0.001)。远端流出道的血管收缩了 31%。同样,10 μM 的奈塔舒利在有小梁网的眼睛(1.91±0.193mmHg,p<0.001)和没有小梁网的眼睛(3.65±0.86mmHg,p<0.001)中升高了 IOP。在这个浓度下,流出道的血管收缩了 27%。

结论

在猪眼前节培养物中,奈塔舒利引起的 IOP 变化与远端流出道血管的直径变化呈剂量依赖性。奈塔舒利的高和低血压特性在去除小梁网后仍然存在。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/613b/7237522/ea944c17054b/417_2020_4691_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/613b/7237522/55510bdf1563/417_2020_4691_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/613b/7237522/3b4870ce65c1/417_2020_4691_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/613b/7237522/a6e443ebdd66/417_2020_4691_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/613b/7237522/ea944c17054b/417_2020_4691_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/613b/7237522/55510bdf1563/417_2020_4691_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/613b/7237522/3b4870ce65c1/417_2020_4691_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/613b/7237522/a6e443ebdd66/417_2020_4691_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/613b/7237522/ea944c17054b/417_2020_4691_Fig4_HTML.jpg

相似文献

1
Dose-dependent effects of netarsudil, a Rho-kinase inhibitor, on the distal outflow tract. Rho 激酶抑制剂奈立定对远端流出道的剂量依赖性作用。
Graefes Arch Clin Exp Ophthalmol. 2020 Jun;258(6):1211-1216. doi: 10.1007/s00417-020-04691-y. Epub 2020 May 5.
2
Visualization of conventional outflow tissue responses to netarsudil in living mouse eyes.活体小鼠眼中传统房水流出组织对奈他地尔反应的可视化。
Eur J Pharmacol. 2016 Sep 15;787:20-31. doi: 10.1016/j.ejphar.2016.04.002. Epub 2016 Apr 13.
3
Netarsudil Improves Trabecular Outflow Facility in Patients with Primary Open Angle Glaucoma or Ocular Hypertension: A Phase 2 Study.奈他舒地尔可改善原发性开角型青光眼或高眼压症患者的小梁流出阻力:一项 2 期研究。
Am J Ophthalmol. 2021 Jun;226:262-269. doi: 10.1016/j.ajo.2021.01.019. Epub 2021 Jan 29.
4
Structure-Function Changes of the Porcine Distal Outflow Tract in Response to Nitric Oxide.猪远心流出道对一氧化氮的结构-功能变化。
Invest Ophthalmol Vis Sci. 2018 Oct 1;59(12):4886-4895. doi: 10.1167/iovs.18-24943.
5
The Effects of Netarsudil Ophthalmic Solution on Aqueous Humor Dynamics in a Randomized Study in Humans.在一项针对人类的随机研究中,奈他舒地尔滴眼液对房水动力学的影响。
J Ocul Pharmacol Ther. 2018 Jun;34(5):380-386. doi: 10.1089/jop.2017.0138. Epub 2018 Feb 22.
6
Netarsudil ophthalmic solution 0.02% for the treatment of patients with open-angle glaucoma or ocular hypertension.0.02%奈他地尔眼药水用于治疗开角型青光眼或高眼压症患者。
Drugs Today (Barc). 2018 Aug;54(8):467-478. doi: 10.1358/dot.2018.54.8.2849627.
7
Two Phase 3 Clinical Trials Comparing the Safety and Efficacy of Netarsudil to Timolol in Patients With Elevated Intraocular Pressure: Rho Kinase Elevated IOP Treatment Trial 1 and 2 (ROCKET-1 and ROCKET-2).两项比较奈立定(netarsudil)和噻吗洛尔(timolol)安全性和疗效的 3 期临床试验: Rho 激酶升高的眼压治疗试验 1 和 2(ROCKET-1 和 ROCKET-2)。
Am J Ophthalmol. 2018 Feb;186:116-127. doi: 10.1016/j.ajo.2017.11.019. Epub 2017 Dec 1.
8
Once-Daily Netarsudil/Latanoprost Fixed-Dose Combination for Elevated Intraocular Pressure in the Randomized Phase 3 MERCURY-2 Study.在随机、3 期 MERCURY-2 研究中,每日一次 netarsudil/拉坦前列素固定剂量组合用于治疗高眼压。
Ophthalmol Glaucoma. 2019 Sep-Oct;2(5):280-289. doi: 10.1016/j.ogla.2019.03.007. Epub 2019 Mar 28.
9
Netarsudil Ophthalmic Solution 0.02%: First Global Approval.奈他舒地尔滴眼液 0.02%:全球首次获批。
Drugs. 2018 Mar;78(3):389-396. doi: 10.1007/s40265-018-0877-7.
10
VEGF-A-induced changes in distal outflow tract structure and function.血管内皮生长因子A(VEGF-A)诱导的远端流出道结构和功能变化。
Graefes Arch Clin Exp Ophthalmol. 2024 Feb;262(2):537-543. doi: 10.1007/s00417-023-06252-5. Epub 2023 Oct 13.

引用本文的文献

1
Endothelial cell-specific postnatal deletion of Nos3 preserves intraocular pressure homeostasis via macrophage recruitment and NOS2 upregulation.出生后内皮细胞特异性缺失Nos3可通过巨噬细胞募集和NOS2上调维持眼内压稳态。
J Clin Invest. 2025 Feb 11;135(7):e183440. doi: 10.1172/JCI183440.
2
Effects of Genipin Crosslinking of Porcine Perilimbal Sclera on Mechanical Properties and Intraocular Pressure.京尼平交联猪角膜缘巩膜对力学性能和眼压的影响
Bioengineering (Basel). 2024 Oct 2;11(10):996. doi: 10.3390/bioengineering11100996.
3
VEGF-A-induced changes in distal outflow tract structure and function.

本文引用的文献

1
A model of the oscillatory mechanical forces in the conventional outflow pathway.传统流出道中振荡机械力的模型。
J R Soc Interface. 2019 Jan 31;16(150):20180652. doi: 10.1098/rsif.2018.0652.
2
Structure-Function Changes of the Porcine Distal Outflow Tract in Response to Nitric Oxide.猪远心流出道对一氧化氮的结构-功能变化。
Invest Ophthalmol Vis Sci. 2018 Oct 1;59(12):4886-4895. doi: 10.1167/iovs.18-24943.
3
Netarsudil ophthalmic solution 0.02% for the treatment of patients with open-angle glaucoma or ocular hypertension.
血管内皮生长因子A(VEGF-A)诱导的远端流出道结构和功能变化。
Graefes Arch Clin Exp Ophthalmol. 2024 Feb;262(2):537-543. doi: 10.1007/s00417-023-06252-5. Epub 2023 Oct 13.
4
Tissue-engineered anterior segment eye cultures demonstrate hallmarks of conventional organ culture.组织工程眼前节眼培养物表现出传统器官培养的特征。
Graefes Arch Clin Exp Ophthalmol. 2023 May;261(5):1359-1368. doi: 10.1007/s00417-022-05915-z. Epub 2022 Dec 24.
5
Trabeculopuncture as a predictive test of distal outflow resistance in canal-based surgery.小梁切开术作为基于管的手术中远端流出阻力的预测性测试。
Sci Rep. 2022 Jun 22;12(1):10584. doi: 10.1038/s41598-022-13990-9.
6
"Rapid and reversible alteration in corneal contour and power associated with Netarsudil/Latanoprost".与奈他地尔/拉坦前列素相关的角膜形态和屈光度的快速可逆改变
Am J Ophthalmol Case Rep. 2022 Mar 25;26:101501. doi: 10.1016/j.ajoc.2022.101501. eCollection 2022 Jun.
7
Effects of Ripasudil on Open-Angle Glaucoma after Circumferential Suture Trabeculotomy Ab Interno.玻璃体内注射瑞帕舒迪对经内路环形小梁切开术后开角型青光眼的影响。
J Clin Med. 2021 Jan 21;10(3):401. doi: 10.3390/jcm10030401.
8
[Rho kinase inhibitors as new local therapy option in primary open angle glaucoma].[ Rho激酶抑制剂作为原发性开角型青光眼的新型局部治疗选择]
Ophthalmologe. 2021 May;118(5):449-460. doi: 10.1007/s00347-020-01303-2. Epub 2021 Jan 5.
9
Exact matching of trabectome-mediated ab interno trabeculectomy to conventional trabeculectomy with mitomycin C followed for 2 years.对小梁切除术介导的内路小梁切除术与丝裂霉素C辅助的传统小梁切除术进行精确匹配,并随访2年。
Graefes Arch Clin Exp Ophthalmol. 2021 Apr;259(4):963-970. doi: 10.1007/s00417-020-05031-w. Epub 2020 Dec 2.
10
Ripasudil in a Model of Pigmentary Glaucoma.在色素性青光眼模型中的瑞帕舒迪
Transl Vis Sci Technol. 2020 Sep 25;9(10):27. doi: 10.1167/tvst.9.10.27. eCollection 2020 Sep.
0.02%奈他地尔眼药水用于治疗开角型青光眼或高眼压症患者。
Drugs Today (Barc). 2018 Aug;54(8):467-478. doi: 10.1358/dot.2018.54.8.2849627.
4
Outflow enhancement by three different ab interno trabeculectomy procedures in a porcine anterior segment model.在猪眼前节模型中三种不同的内路小梁切除术对房水流出的增强作用。
Graefes Arch Clin Exp Ophthalmol. 2018 Jul;256(7):1305-1312. doi: 10.1007/s00417-018-3990-0. Epub 2018 May 2.
5
Pharmacological regulation of outflow resistance distal to Schlemm's canal.房水流出阻力施莱姆管远端的药理学调节。
Am J Physiol Cell Physiol. 2018 Jul 1;315(1):C44-C51. doi: 10.1152/ajpcell.00024.2018. Epub 2018 Apr 6.
6
The Effects of Netarsudil Ophthalmic Solution on Aqueous Humor Dynamics in a Randomized Study in Humans.在一项针对人类的随机研究中,奈他舒地尔滴眼液对房水动力学的影响。
J Ocul Pharmacol Ther. 2018 Jun;34(5):380-386. doi: 10.1089/jop.2017.0138. Epub 2018 Feb 22.
7
Two Phase 3 Clinical Trials Comparing the Safety and Efficacy of Netarsudil to Timolol in Patients With Elevated Intraocular Pressure: Rho Kinase Elevated IOP Treatment Trial 1 and 2 (ROCKET-1 and ROCKET-2).两项比较奈立定(netarsudil)和噻吗洛尔(timolol)安全性和疗效的 3 期临床试验: Rho 激酶升高的眼压治疗试验 1 和 2(ROCKET-1 和 ROCKET-2)。
Am J Ophthalmol. 2018 Feb;186:116-127. doi: 10.1016/j.ajo.2017.11.019. Epub 2017 Dec 1.
8
Comparative Study of the Effects of Trabecular Meshwork Outflow Drugs on the Permeability and Nitric Oxide Production in Trabecular Meshwork Cells.小梁网流出药物对小梁网细胞通透性和一氧化氮生成影响的比较研究
Korean J Ophthalmol. 2017 Oct;31(5):452-459. doi: 10.3341/kjo.2017.0020. Epub 2017 Jul 25.
9
Discovery and Preclinical Development of Netarsudil, a Novel Ocular Hypotensive Agent for the Treatment of Glaucoma.发现和临床前开发新型眼部降眼压剂奈他舒地尔治疗青光眼。
J Ocul Pharmacol Ther. 2018 Jan/Feb;34(1-2):40-51. doi: 10.1089/jop.2017.0023. Epub 2017 Jun 13.
10
Training strategies and outcomes of trabeculectomy with the trabectome.使用小梁切除术器械进行小梁切除术的训练策略及结果
F1000Res. 2017 Jan 23;6:67. doi: 10.12688/f1000research.10236.2. eCollection 2017.