Nrf2-HO1 signaling pathway-mediated axial elongation in lens-induced myopia in Guinea pigs through regulation of tight junctions in retinal pigment epithelial cells

IF 3 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research Pub Date : 2025-06-04 DOI:10.1016/j.exer.2025.110477

He-Yan Li , Li Dong , Rui-Heng Zhang , Wen-Da Zhou , Hao-Tian Wu , Xu-Han Shi , Chu-Yao Yu , Yi-Tong Li , Jost B. Jonas , Wen-Bin Wei

{"title":"Nrf2-HO1 signaling pathway-mediated axial elongation in lens-induced myopia in Guinea pigs through regulation of tight junctions in retinal pigment epithelial cells","authors":"He-Yan Li , Li Dong , Rui-Heng Zhang , Wen-Da Zhou , Hao-Tian Wu , Xu-Han Shi , Chu-Yao Yu , Yi-Tong Li , Jost B. Jonas , Wen-Bin Wei","doi":"10.1016/j.exer.2025.110477","DOIUrl":null,"url":null,"abstract":"<div><div>The study aimed to explore the potential involvement of Nrf2-HO1 (nuclear factor erythroid 2-related factor 2 heme oxygenase-1) in the process of myopic axial elongation, which influenced the disruption of tight junctions in retinal pigment epithelium (RPE) cells. Guinea pigs aged 2–3 weeks underwent bilateral lens-induced myopization (LIM) and received weekly intraperitoneal injections of the heme oxygenase-1 (HO-1) activators Hemin (25 mg/kg and 50 mg/kg, respectively), or Quercetin (25 mg/kg and 50 mg/kg, respectively). The study additionally included normal control groups with or without LIM and with vehicle injections. Ocular biometry, optical coherence tomography, and high-throughput sequencing were performed. Eyes with LIM showed a significantly increased expression of the Nrf2-HO1 signal pathway. Eyes with Hemin injections demonstrated axial elongation in a Hemin-dose dependent manner. Eyes with LIM and Quercetin injections showed in a dose-dependent manner and inhibition of the Nrf2 overexpression and an attenuation of axial elongation, a disruption of RPE cell tight junctions, and retinal and choroidal thinning. Immunofluorescence revealed the RPE cell as the main location of the HO-1 activation. Transmission electron microscope showed that Hemin was associated with a disruption of RPE tight junctions with axial elongation. The overexpression of Nrf2-HO1 signal pathway may be involved in LIM development and RPE tight junction disruption. The potential anti-myopic therapeutic value of Quercetin may be further explored.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"258 ","pages":"Article 110477"},"PeriodicalIF":3.0000,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Experimental eye research","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0014483525002489","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

The study aimed to explore the potential involvement of Nrf2-HO1 (nuclear factor erythroid 2-related factor 2 heme oxygenase-1) in the process of myopic axial elongation, which influenced the disruption of tight junctions in retinal pigment epithelium (RPE) cells. Guinea pigs aged 2–3 weeks underwent bilateral lens-induced myopization (LIM) and received weekly intraperitoneal injections of the heme oxygenase-1 (HO-1) activators Hemin (25 mg/kg and 50 mg/kg, respectively), or Quercetin (25 mg/kg and 50 mg/kg, respectively). The study additionally included normal control groups with or without LIM and with vehicle injections. Ocular biometry, optical coherence tomography, and high-throughput sequencing were performed. Eyes with LIM showed a significantly increased expression of the Nrf2-HO1 signal pathway. Eyes with Hemin injections demonstrated axial elongation in a Hemin-dose dependent manner. Eyes with LIM and Quercetin injections showed in a dose-dependent manner and inhibition of the Nrf2 overexpression and an attenuation of axial elongation, a disruption of RPE cell tight junctions, and retinal and choroidal thinning. Immunofluorescence revealed the RPE cell as the main location of the HO-1 activation. Transmission electron microscope showed that Hemin was associated with a disruption of RPE tight junctions with axial elongation. The overexpression of Nrf2-HO1 signal pathway may be involved in LIM development and RPE tight junction disruption. The potential anti-myopic therapeutic value of Quercetin may be further explored.

查看原文本刊更多论文

Nrf2-HO1信号通路通过调节视网膜色素上皮细胞的紧密连接介导豚鼠晶状体性近视的轴向伸长

本研究旨在探讨Nrf2-HO1（核因子红系2相关因子2血红素加氧酶-1）在近视轴向伸长过程中可能参与，影响视网膜色素上皮（RPE）细胞紧密连接的破坏。2-3周龄的豚鼠接受双侧晶状体诱导近视（LIM），每周腹腔注射血红素加氧酶-1 （HO-1）激活剂Hemin（分别为25 mg/kg和50 mg/kg）或槲皮素（分别为25 mg/kg和50 mg/kg）。该研究还包括有或没有LIM和车辆注射的正常对照组。进行眼生物测量、光学相干断层扫描和高通量测序。LIM眼Nrf2-HO1信号通路的表达明显增加。用血红蛋白注射的眼睛表现出以血红蛋白剂量依赖的轴向伸长。注射LIM和槲皮素的眼睛显示出剂量依赖性，Nrf2过表达受到抑制，轴向伸长衰减，RPE细胞紧密连接被破坏，视网膜和脉络膜变薄。免疫荧光显示RPE细胞是HO-1激活的主要部位。透射电镜显示，Hemin与RPE紧密连接的破坏与轴向伸长有关。Nrf2-HO1信号通路的过表达可能参与了LIM的发生和RPE紧密连接的破坏。槲皮素抗近视的潜在治疗价值有待进一步挖掘。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Experimental eye research 医学-眼科学

CiteScore

6.80

自引率

5.90%

发文量

323

审稿时长

66 days

期刊介绍： The primary goal of Experimental Eye Research is to publish original research papers on all aspects of experimental biology of the eye and ocular tissues that seek to define the mechanisms of normal function and/or disease. Studies of ocular tissues that encompass the disciplines of cell biology, developmental biology, genetics, molecular biology, physiology, biochemistry, biophysics, immunology or microbiology are most welcomed. Manuscripts that are purely clinical or in a surgical area of ophthalmology are not appropriate for submission to Experimental Eye Research and if received will be returned without review.