Carbonic anhydrase inhibitor alleviates retinal barrier toxicity in paclitaxel-induced retinopathy and macular edema by inhibiting CAXIV.

IF 1.4 4区医学 Q3 OPHTHALMOLOGY

International Ophthalmology Pub Date : 2024-11-23 DOI:10.1007/s10792-024-03362-9

Ya-Ting Ye, Ya-Li Niu, Zi-Yi Zhou, Yu Sun, Tian-Fang Chang, Yu-Tong Jing, Qian Bai, Zhao-Jie Chu

{"title":"Carbonic anhydrase inhibitor alleviates retinal barrier toxicity in paclitaxel-induced retinopathy and macular edema by inhibiting CAXIV.","authors":"Ya-Ting Ye, Ya-Li Niu, Zi-Yi Zhou, Yu Sun, Tian-Fang Chang, Yu-Tong Jing, Qian Bai, Zhao-Jie Chu","doi":"10.1007/s10792-024-03362-9","DOIUrl":null,"url":null,"abstract":"Purpose: To investigate the mechanism of paclitaxel (PTX)-induced macular edema and the therapeutic effect of carbonic anhydrase inhibitors (CAI) on this condition.Methods: The effect of PTX on cell morphology was detected by immunofluorescence. Cell barrier was measured by measuring cell resistance across the epithelium. Western blotting analysis and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were performed to investigate the effects of PTX or PTX + CAI on the expression of carbonic anhydrase XIV (CAXIV), aquaporin 4 (AQP4) and inflammatory factors. After intraperitoneal injection of PTX in vivo, retinal electrophysiology (ERG) was used to evaluate the effects of drugs on visual electrophysiology.Results: PTX inhibited the proliferation of ARPE-19 and Müller cells, promoting their apoptosis, changing their morphology and cell cycle, reducing the transepithelial resistance of ARPE-19 cells and promoting the expression of inflammatory factors; This process was alleviated after temporary withdrawal. CAI inhibited the upregulation of inflammatory factors. Following treatment with PTX, the expression levels of AQP4 and CAXIV were higher than control group; nevertheless, the levels of ZO-1 and OCLN were lower than control group. In vivo, the ERG analysis showed that the light- and dark-adapted 3.0 ERG, and dark-adapted 3.0 oscillatory potentials decreased to different degrees following treatment with PTX.Conclusion: PTX-induced macular edema is mainly due to Müller cell toxicity. The condition can be alleviated by regulating water channels and enhancing subretinal fluid absorption. Thus, CAI may provide a new therapeutic approach for PTX-induced macular edema.","PeriodicalId":14473,"journal":{"name":"International Ophthalmology","volume":"44 1","pages":"437"},"PeriodicalIF":1.4000,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11584476/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Ophthalmology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10792-024-03362-9","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Purpose: To investigate the mechanism of paclitaxel (PTX)-induced macular edema and the therapeutic effect of carbonic anhydrase inhibitors (CAI) on this condition.

Methods: The effect of PTX on cell morphology was detected by immunofluorescence. Cell barrier was measured by measuring cell resistance across the epithelium. Western blotting analysis and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were performed to investigate the effects of PTX or PTX + CAI on the expression of carbonic anhydrase XIV (CAXIV), aquaporin 4 (AQP4) and inflammatory factors. After intraperitoneal injection of PTX in vivo, retinal electrophysiology (ERG) was used to evaluate the effects of drugs on visual electrophysiology.

Results: PTX inhibited the proliferation of ARPE-19 and Müller cells, promoting their apoptosis, changing their morphology and cell cycle, reducing the transepithelial resistance of ARPE-19 cells and promoting the expression of inflammatory factors; This process was alleviated after temporary withdrawal. CAI inhibited the upregulation of inflammatory factors. Following treatment with PTX, the expression levels of AQP4 and CAXIV were higher than control group; nevertheless, the levels of ZO-1 and OCLN were lower than control group. In vivo, the ERG analysis showed that the light- and dark-adapted 3.0 ERG, and dark-adapted 3.0 oscillatory potentials decreased to different degrees following treatment with PTX.

Conclusion: PTX-induced macular edema is mainly due to Müller cell toxicity. The condition can be alleviated by regulating water channels and enhancing subretinal fluid absorption. Thus, CAI may provide a new therapeutic approach for PTX-induced macular edema.

查看原文本刊更多论文

碳酸酐酶抑制剂通过抑制 CAXIV 减轻紫杉醇诱导的视网膜病变和黄斑水肿的视网膜屏障毒性。

目的：研究紫杉醇（PTX）诱导黄斑水肿的机制以及碳酸酐酶抑制剂（CAI）对该病症的治疗效果：方法：用免疫荧光法检测PTX对细胞形态的影响。通过测量细胞穿过上皮细胞的阻力来测量细胞屏障。进行了 Western 印迹分析和逆转录-定量聚合酶链反应（RT-qPCR），以研究 PTX 或 PTX + CAI 对碳酸酐酶 XIV（CAXIV）、水蒸发素 4（AQP4）和炎症因子表达的影响。腹腔注射PTX后，用视网膜电生理学（ERG）评估药物对视觉电生理学的影响：结果：PTX抑制ARPE-19和Müller细胞的增殖，促进其凋亡，改变其形态和细胞周期，降低ARPE-19细胞的跨上皮阻力，促进炎症因子的表达；暂时停药后这一过程得到缓解。CAI 抑制了炎症因子的上调。PTX 治疗后，AQP4 和 CAXIV 的表达水平高于对照组；但 ZO-1 和 OCLN 的表达水平低于对照组。体内ERG分析显示，PTX治疗后，明暗适应3.0 ERG和暗适应3.0振荡电位均有不同程度的下降：结论：PTX诱导的黄斑水肿主要是由于Müller细胞毒性所致。结论：PTX 引起的黄斑水肿主要是由于 Müller 细胞毒性所致，可以通过调节水通道和促进视网膜下液体吸收来缓解病情。因此，CAI 可为 PTX 引起的黄斑水肿提供一种新的治疗方法。

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

International Ophthalmology OPHTHALMOLOGY-

CiteScore

3.20

自引率

0.00%

发文量

451

期刊介绍： International Ophthalmology provides the clinician with articles on all the relevant subspecialties of ophthalmology, with a broad international scope. The emphasis is on presentation of the latest clinical research in the field. In addition, the journal includes regular sections devoted to new developments in technologies, products, and techniques.