Yuting Li , Cong Han , Jianping Zhang , Songjian Huang , Xin Zhao , Jiarui Zhu , Qian Niu , Yi Yang , Wenfang Zhang
{"title":"急性高海拔暴露时视网膜小胶质细胞的激活和迁移","authors":"Yuting Li , Cong Han , Jianping Zhang , Songjian Huang , Xin Zhao , Jiarui Zhu , Qian Niu , Yi Yang , Wenfang Zhang","doi":"10.1016/j.exer.2025.110653","DOIUrl":null,"url":null,"abstract":"<div><div>High-altitude retinopathy (HAR), caused by hypobaric hypoxia, leads to retinal dysfunction. However, its pathogenic mechanism remains elusive. Microglia, the resident immune cells of the retina, play crucial roles in various retinal disorders. Here, we investigated the functional alterations and underlying mechanisms of microglial activation in mouse models exposed to high-altitude (5000m HAE). Hematoxylin and eosin (H&E) staining showed edema in the entire, inner, and outer retinal layers after high-altitude exposure (HAE). Electroretinogram (ERG) testing revealed impaired retinal function under hypobaric hypoxia. Immunofluorescence staining confirmed a time-dependent increase in microglial numbers within the retina following HAE, with activated microglia migrating during persistent hypoxic injury. Furthermore, these activated microglia predominantly differentiated into pro-inflammatory subtypes under acute high-altitude conditions. Notably, Connexin43 (Cx43) immunoreactivity increased, while interleukin-1β (IL-1β) levels were markedly elevated at different time points after HAE. In this study, we confirmed that microglia activation and migration are involved in retinal edema and functional injury induced by hypobaric hypoxia. Additionally, the dynamic changes in Cx43 and up-regulation of IL-1β might be related to the inflammatory activation of microglia under acute HAE.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"261 ","pages":"Article 110653"},"PeriodicalIF":2.7000,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Microglia activation and migration in retina during acute high-altitude exposure\",\"authors\":\"Yuting Li , Cong Han , Jianping Zhang , Songjian Huang , Xin Zhao , Jiarui Zhu , Qian Niu , Yi Yang , Wenfang Zhang\",\"doi\":\"10.1016/j.exer.2025.110653\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>High-altitude retinopathy (HAR), caused by hypobaric hypoxia, leads to retinal dysfunction. However, its pathogenic mechanism remains elusive. Microglia, the resident immune cells of the retina, play crucial roles in various retinal disorders. Here, we investigated the functional alterations and underlying mechanisms of microglial activation in mouse models exposed to high-altitude (5000m HAE). Hematoxylin and eosin (H&E) staining showed edema in the entire, inner, and outer retinal layers after high-altitude exposure (HAE). Electroretinogram (ERG) testing revealed impaired retinal function under hypobaric hypoxia. Immunofluorescence staining confirmed a time-dependent increase in microglial numbers within the retina following HAE, with activated microglia migrating during persistent hypoxic injury. Furthermore, these activated microglia predominantly differentiated into pro-inflammatory subtypes under acute high-altitude conditions. Notably, Connexin43 (Cx43) immunoreactivity increased, while interleukin-1β (IL-1β) levels were markedly elevated at different time points after HAE. In this study, we confirmed that microglia activation and migration are involved in retinal edema and functional injury induced by hypobaric hypoxia. Additionally, the dynamic changes in Cx43 and up-regulation of IL-1β might be related to the inflammatory activation of microglia under acute HAE.</div></div>\",\"PeriodicalId\":12177,\"journal\":{\"name\":\"Experimental eye research\",\"volume\":\"261 \",\"pages\":\"Article 110653\"},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2025-09-23\",\"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/S0014483525004257\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"OPHTHALMOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Experimental eye research","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0014483525004257","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}
Microglia activation and migration in retina during acute high-altitude exposure
High-altitude retinopathy (HAR), caused by hypobaric hypoxia, leads to retinal dysfunction. However, its pathogenic mechanism remains elusive. Microglia, the resident immune cells of the retina, play crucial roles in various retinal disorders. Here, we investigated the functional alterations and underlying mechanisms of microglial activation in mouse models exposed to high-altitude (5000m HAE). Hematoxylin and eosin (H&E) staining showed edema in the entire, inner, and outer retinal layers after high-altitude exposure (HAE). Electroretinogram (ERG) testing revealed impaired retinal function under hypobaric hypoxia. Immunofluorescence staining confirmed a time-dependent increase in microglial numbers within the retina following HAE, with activated microglia migrating during persistent hypoxic injury. Furthermore, these activated microglia predominantly differentiated into pro-inflammatory subtypes under acute high-altitude conditions. Notably, Connexin43 (Cx43) immunoreactivity increased, while interleukin-1β (IL-1β) levels were markedly elevated at different time points after HAE. In this study, we confirmed that microglia activation and migration are involved in retinal edema and functional injury induced by hypobaric hypoxia. Additionally, the dynamic changes in Cx43 and up-regulation of IL-1β might be related to the inflammatory activation of microglia under acute HAE.
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.