Oridonin Preserves Retinal Pigmented Epithelial Cell Tight Junctions and Ameliorates Choroidal Neovascularization.

IF 5 2区医学 Q1 OPHTHALMOLOGY

Investigative ophthalmology & visual science Pub Date : 2025-02-03 DOI:10.1167/iovs.66.2.56

Juming Zhu, Dongmei Ding, Tao Sun, Yuting Zhang, Huizi Miao, Yunjie Gu, Ming Dai, Manhui Zhu

{"title":"Oridonin Preserves Retinal Pigmented Epithelial Cell Tight Junctions and Ameliorates Choroidal Neovascularization.","authors":"Juming Zhu, Dongmei Ding, Tao Sun, Yuting Zhang, Huizi Miao, Yunjie Gu, Ming Dai, Manhui Zhu","doi":"10.1167/iovs.66.2.56","DOIUrl":null,"url":null,"abstract":"Purpose: To investigate the role and mechanism of oridonin (ORI), a bioactive diterpenoid extracted from the Chinese herbal medicine Rabdosia rubescens, on the integrity of outer blood-retinal barrier (oBRB) during choroidal neovascularization (CNV).Methods: ARPE-19 cells were exposed to hypoxia and treated with ORI. The expression of ZO-1 and occludin in the axis of TGFβR/SUV39H1/KLF11 was detected by WB, chromatin immunoprecipitation, luciferin report activity assay, and immunofluorescence assay (IF), and the effect of ORI on the barrier properties of ARPE-19 cells was studied. A laser-induced mouse CNV model was constructed, and ORI was administrated by oral gavage. IF on mouse choroid flat mounts was done to confirm the effect of ORI on BRB integrity. Indocyanine green angiography and IF on mouse retina-RPE-choroid flat mounts were performed to determine the effect of ORI on CNV formation and retinal function. Hematoxylin and eosin staining and TUNEL staining were carried out to appraise ocular and systemic cytotoxicity caused by ORI.Results: ORI protected ARPE-19 cells from hypoxia-induced destruction of barrier properties and promoted the expression of ZO-1 and occludin by the TGFβR/SUV39H1/KLF11 axis, maintaining barrier properties of ARPE-19 cells with hypoxia. ORI improved BRB integrity during laser-induced CNV in mice and mitigated laser-induced CNV formation in mice without any ocular or systemic cytotoxicity (n = 4-5 in each group).Conclusions: ORI ameliorates BRB integrity and subsequent formation of CNV via regulating the TGFβR/SUV39H1/KLF11 pathway in RPE cells.","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 2","pages":"56"},"PeriodicalIF":5.0000,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11855140/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Investigative ophthalmology & visual science","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1167/iovs.66.2.56","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

Purpose: To investigate the role and mechanism of oridonin (ORI), a bioactive diterpenoid extracted from the Chinese herbal medicine Rabdosia rubescens, on the integrity of outer blood-retinal barrier (oBRB) during choroidal neovascularization (CNV).

Methods: ARPE-19 cells were exposed to hypoxia and treated with ORI. The expression of ZO-1 and occludin in the axis of TGFβR/SUV39H1/KLF11 was detected by WB, chromatin immunoprecipitation, luciferin report activity assay, and immunofluorescence assay (IF), and the effect of ORI on the barrier properties of ARPE-19 cells was studied. A laser-induced mouse CNV model was constructed, and ORI was administrated by oral gavage. IF on mouse choroid flat mounts was done to confirm the effect of ORI on BRB integrity. Indocyanine green angiography and IF on mouse retina-RPE-choroid flat mounts were performed to determine the effect of ORI on CNV formation and retinal function. Hematoxylin and eosin staining and TUNEL staining were carried out to appraise ocular and systemic cytotoxicity caused by ORI.

Results: ORI protected ARPE-19 cells from hypoxia-induced destruction of barrier properties and promoted the expression of ZO-1 and occludin by the TGFβR/SUV39H1/KLF11 axis, maintaining barrier properties of ARPE-19 cells with hypoxia. ORI improved BRB integrity during laser-induced CNV in mice and mitigated laser-induced CNV formation in mice without any ocular or systemic cytotoxicity (n = 4-5 in each group).

Conclusions: ORI ameliorates BRB integrity and subsequent formation of CNV via regulating the TGFβR/SUV39H1/KLF11 pathway in RPE cells.

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Investigative ophthalmology & visual science 医学-眼科学

CiteScore

6.90

自引率

4.50%

发文量

339

审稿时长

1 months

期刊介绍： Investigative Ophthalmology & Visual Science (IOVS), published as ready online, is a peer-reviewed academic journal of the Association for Research in Vision and Ophthalmology (ARVO). IOVS features original research, mostly pertaining to clinical and laboratory ophthalmology and vision research in general.