Hitomi Yagi, Myriam Boeck, Mariya Petrishka-Lozenska, Pia Lundgren, Taku Kasai, Gael Cagnone, Katherine Neilsen, Chaomei Wang, Jeff Lee, Yohei Tomita, Sasha A. Singh, Jean-Sébastien Joyal, Masanori Aikawa, Kazuno Negishi, Zhongjie Fu, Ann Hellström, Lois E.H. Smith
{"title":"定时局部使用地塞米松滴眼液可改善线粒体功能,预防严重的早产儿视网膜病变","authors":"Hitomi Yagi, Myriam Boeck, Mariya Petrishka-Lozenska, Pia Lundgren, Taku Kasai, Gael Cagnone, Katherine Neilsen, Chaomei Wang, Jeff Lee, Yohei Tomita, Sasha A. Singh, Jean-Sébastien Joyal, Masanori Aikawa, Kazuno Negishi, Zhongjie Fu, Ann Hellström, Lois E.H. Smith","doi":"10.1007/s10456-024-09948-2","DOIUrl":null,"url":null,"abstract":"<p>Pathological neovascularization in retinopathy of prematurity (ROP) can cause visual impairment in preterm infants. Current ROP treatments which are not preventative and only address late neovascular ROP, are costly and can lead to severe complications. We showed that topical 0.1% dexamethasone eye drops administered prior to peak neovessel formation prevented neovascularization in five extremely preterm infants at high risk for ROP and suppressed neovascularization by 30% in mouse oxygen-induced retinopathy (OIR) modeling ROP. In contrast, in OIR, topical dexamethasone treatment before any neovessel formation had limited efficacy in preventing later neovascularization, while treatment after peak neovessel formation had a non-statistically significant trend to exacerbating disease. Optimally timed topical dexamethasone suppression of neovascularization in OIR was associated with increased retinal mitochondrial gene expression and decreased inflammatory marker expression, predominantly found in immune cells. Blocking mitochondrial ATP synthetase reversed the inhibitory effect of dexamethasone on neovascularization in OIR. This study provides new insights into topical steroid effects in retinal neovascularization and into mitochondrial function in phase II ROP, and suggests a simple clinical approach to prevent severe ROP.</p>","PeriodicalId":7886,"journal":{"name":"Angiogenesis","volume":null,"pages":null},"PeriodicalIF":9.2000,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Timed topical dexamethasone eye drops improve mitochondrial function to prevent severe retinopathy of prematurity\",\"authors\":\"Hitomi Yagi, Myriam Boeck, Mariya Petrishka-Lozenska, Pia Lundgren, Taku Kasai, Gael Cagnone, Katherine Neilsen, Chaomei Wang, Jeff Lee, Yohei Tomita, Sasha A. Singh, Jean-Sébastien Joyal, Masanori Aikawa, Kazuno Negishi, Zhongjie Fu, Ann Hellström, Lois E.H. Smith\",\"doi\":\"10.1007/s10456-024-09948-2\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Pathological neovascularization in retinopathy of prematurity (ROP) can cause visual impairment in preterm infants. Current ROP treatments which are not preventative and only address late neovascular ROP, are costly and can lead to severe complications. We showed that topical 0.1% dexamethasone eye drops administered prior to peak neovessel formation prevented neovascularization in five extremely preterm infants at high risk for ROP and suppressed neovascularization by 30% in mouse oxygen-induced retinopathy (OIR) modeling ROP. In contrast, in OIR, topical dexamethasone treatment before any neovessel formation had limited efficacy in preventing later neovascularization, while treatment after peak neovessel formation had a non-statistically significant trend to exacerbating disease. Optimally timed topical dexamethasone suppression of neovascularization in OIR was associated with increased retinal mitochondrial gene expression and decreased inflammatory marker expression, predominantly found in immune cells. Blocking mitochondrial ATP synthetase reversed the inhibitory effect of dexamethasone on neovascularization in OIR. This study provides new insights into topical steroid effects in retinal neovascularization and into mitochondrial function in phase II ROP, and suggests a simple clinical approach to prevent severe ROP.</p>\",\"PeriodicalId\":7886,\"journal\":{\"name\":\"Angiogenesis\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":9.2000,\"publicationDate\":\"2024-09-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Angiogenesis\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s10456-024-09948-2\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PERIPHERAL VASCULAR DISEASE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Angiogenesis","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10456-024-09948-2","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PERIPHERAL VASCULAR DISEASE","Score":null,"Total":0}
Timed topical dexamethasone eye drops improve mitochondrial function to prevent severe retinopathy of prematurity
Pathological neovascularization in retinopathy of prematurity (ROP) can cause visual impairment in preterm infants. Current ROP treatments which are not preventative and only address late neovascular ROP, are costly and can lead to severe complications. We showed that topical 0.1% dexamethasone eye drops administered prior to peak neovessel formation prevented neovascularization in five extremely preterm infants at high risk for ROP and suppressed neovascularization by 30% in mouse oxygen-induced retinopathy (OIR) modeling ROP. In contrast, in OIR, topical dexamethasone treatment before any neovessel formation had limited efficacy in preventing later neovascularization, while treatment after peak neovessel formation had a non-statistically significant trend to exacerbating disease. Optimally timed topical dexamethasone suppression of neovascularization in OIR was associated with increased retinal mitochondrial gene expression and decreased inflammatory marker expression, predominantly found in immune cells. Blocking mitochondrial ATP synthetase reversed the inhibitory effect of dexamethasone on neovascularization in OIR. This study provides new insights into topical steroid effects in retinal neovascularization and into mitochondrial function in phase II ROP, and suggests a simple clinical approach to prevent severe ROP.
期刊介绍:
Angiogenesis, a renowned international journal, seeks to publish high-quality original articles and reviews on the cellular and molecular mechanisms governing angiogenesis in both normal and pathological conditions. By serving as a primary platform for swift communication within the field of angiogenesis research, this multidisciplinary journal showcases pioneering experimental studies utilizing molecular techniques, in vitro methods, animal models, and clinical investigations into angiogenic diseases. Furthermore, Angiogenesis sheds light on cutting-edge therapeutic strategies for promoting or inhibiting angiogenesis, while also highlighting fresh markers and techniques for disease diagnosis and prognosis.