{"title":"Pharmacological regulation of HIF-1α, RGC death, and glaucoma","authors":"Shahid Husain, Ryan Leveckis","doi":"10.1016/j.coph.2024.102467","DOIUrl":null,"url":null,"abstract":"<div><p>Hypoxia can regulate oxygen-sensitive pathways that could be neuroprotective to compensate for the detrimental effects of low oxygen. However, prolonged hypoxia can activate neurodegenerative pathways. HIF-1α is upregulated/stabilized in hypoxic conditions, promoting alteration of gene expression, and ultimately leading to cell-death. Therefore, regulation of HIF-1α expression pharmacologically is a vital approach to mitigate cell death. In this review, we provide information showing the role of HIF-1α and its associated pathways in ocular retinopathies. We also discuss the beneficial roles of HIF-1α inhibitor, KC7F2, in ocular pathologies. Finally, we provided our own data demonstrating RGC neuroprotection by KC7F2 in glaucomatous animals.</p></div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":null,"pages":null},"PeriodicalIF":4.0000,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Opinion in Pharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1471489224000377","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Hypoxia can regulate oxygen-sensitive pathways that could be neuroprotective to compensate for the detrimental effects of low oxygen. However, prolonged hypoxia can activate neurodegenerative pathways. HIF-1α is upregulated/stabilized in hypoxic conditions, promoting alteration of gene expression, and ultimately leading to cell-death. Therefore, regulation of HIF-1α expression pharmacologically is a vital approach to mitigate cell death. In this review, we provide information showing the role of HIF-1α and its associated pathways in ocular retinopathies. We also discuss the beneficial roles of HIF-1α inhibitor, KC7F2, in ocular pathologies. Finally, we provided our own data demonstrating RGC neuroprotection by KC7F2 in glaucomatous animals.
期刊介绍:
Current Opinion in Pharmacology (COPHAR) publishes authoritative, comprehensive, and systematic reviews. COPHAR helps specialists keep up to date with a clear and readable synthesis on current advances in pharmacology and drug discovery. Expert authors annotate the most interesting papers from the expanding volume of information published today, saving valuable time and giving the reader insight on areas of importance.