Eric Engelbrecht, Melissa A. Metzler, Lisa L. Sandell
{"title":"类视黄醇信号调节新生小鼠视网膜血管生成和血视网膜屏障完整性","authors":"Eric Engelbrecht, Melissa A. Metzler, Lisa L. Sandell","doi":"10.1111/micc.12752","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Objective</h3>\n \n <p>The neonatal mouse retina is a well-characterized experimental model for investigating factors impacting retinal angiogenesis and inner blood-retinal barrier (BRB) integrity. Retinoic acid (RA) is an essential signaling molecule. RA is needed for vasculogenic development in embryos and endothelial barrier integrity in zebrafish retina and adult mouse brain; however, the function of this signaling molecule in developing mammalian retinal vasculature remains unknown. This study aims to investigate the role of RA signaling in angiogenesis and inner BRB integrity in mouse neonatal retina.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>RA distribution in the developing neurovascular retina was assessed in mice carrying an RA-responsive transgene. RA function in retinal angiogenesis was determined by treating C57BL/6 neonatal pups with a pharmacological inhibitor of RA signaling BMS493 or control vehicle. BRB integrity assessed by monitoring leakage of injected tracer into extravascular retinal tissue.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>RA signaling activity is present in peripheral astrocytes in domains corresponding to RA activity of the underlying neural retina. RA inhibition impaired retinal angiogenesis and reduced endothelial cell proliferation. RA inhibition also compromised BRB integrity. Vascular leakage was not associated with altered expression of CLDN5, PLVAP, LEF1, or VEcad.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>RA signaling is needed for angiogenesis and integrity of the BRB in the neonatal mouse retina.</p>\n </section>\n </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":null,"pages":null},"PeriodicalIF":1.9000,"publicationDate":"2022-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.12752","citationCount":"3","resultStr":"{\"title\":\"Retinoid signaling regulates angiogenesis and blood-retinal barrier integrity in neonatal mouse retina\",\"authors\":\"Eric Engelbrecht, Melissa A. Metzler, Lisa L. Sandell\",\"doi\":\"10.1111/micc.12752\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Objective</h3>\\n \\n <p>The neonatal mouse retina is a well-characterized experimental model for investigating factors impacting retinal angiogenesis and inner blood-retinal barrier (BRB) integrity. Retinoic acid (RA) is an essential signaling molecule. RA is needed for vasculogenic development in embryos and endothelial barrier integrity in zebrafish retina and adult mouse brain; however, the function of this signaling molecule in developing mammalian retinal vasculature remains unknown. This study aims to investigate the role of RA signaling in angiogenesis and inner BRB integrity in mouse neonatal retina.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>RA distribution in the developing neurovascular retina was assessed in mice carrying an RA-responsive transgene. RA function in retinal angiogenesis was determined by treating C57BL/6 neonatal pups with a pharmacological inhibitor of RA signaling BMS493 or control vehicle. BRB integrity assessed by monitoring leakage of injected tracer into extravascular retinal tissue.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>RA signaling activity is present in peripheral astrocytes in domains corresponding to RA activity of the underlying neural retina. RA inhibition impaired retinal angiogenesis and reduced endothelial cell proliferation. RA inhibition also compromised BRB integrity. Vascular leakage was not associated with altered expression of CLDN5, PLVAP, LEF1, or VEcad.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>RA signaling is needed for angiogenesis and integrity of the BRB in the neonatal mouse retina.</p>\\n </section>\\n </div>\",\"PeriodicalId\":18459,\"journal\":{\"name\":\"Microcirculation\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2022-02-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.12752\",\"citationCount\":\"3\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Microcirculation\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/micc.12752\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Microcirculation","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/micc.12752","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"HEMATOLOGY","Score":null,"Total":0}
Retinoid signaling regulates angiogenesis and blood-retinal barrier integrity in neonatal mouse retina
Objective
The neonatal mouse retina is a well-characterized experimental model for investigating factors impacting retinal angiogenesis and inner blood-retinal barrier (BRB) integrity. Retinoic acid (RA) is an essential signaling molecule. RA is needed for vasculogenic development in embryos and endothelial barrier integrity in zebrafish retina and adult mouse brain; however, the function of this signaling molecule in developing mammalian retinal vasculature remains unknown. This study aims to investigate the role of RA signaling in angiogenesis and inner BRB integrity in mouse neonatal retina.
Methods
RA distribution in the developing neurovascular retina was assessed in mice carrying an RA-responsive transgene. RA function in retinal angiogenesis was determined by treating C57BL/6 neonatal pups with a pharmacological inhibitor of RA signaling BMS493 or control vehicle. BRB integrity assessed by monitoring leakage of injected tracer into extravascular retinal tissue.
Results
RA signaling activity is present in peripheral astrocytes in domains corresponding to RA activity of the underlying neural retina. RA inhibition impaired retinal angiogenesis and reduced endothelial cell proliferation. RA inhibition also compromised BRB integrity. Vascular leakage was not associated with altered expression of CLDN5, PLVAP, LEF1, or VEcad.
Conclusions
RA signaling is needed for angiogenesis and integrity of the BRB in the neonatal mouse retina.
期刊介绍：
The journal features original contributions that are the result of investigations contributing significant new information relating to the vascular and lymphatic microcirculation addressed at the intact animal, organ, cellular, or molecular level. Papers describe applications of the methods of physiology, biophysics, bioengineering, genetics, cell biology, biochemistry, and molecular biology to problems in microcirculation.
Microcirculation also publishes state-of-the-art reviews that address frontier areas or new advances in technology in the fields of microcirculatory disease and function. Specific areas of interest include: Angiogenesis, growth and remodeling; Transport and exchange of gasses and solutes; Rheology and biorheology; Endothelial cell biology and metabolism; Interactions between endothelium, smooth muscle, parenchymal cells, leukocytes and platelets; Regulation of vasomotor tone; and Microvascular structures, imaging and morphometry. Papers also describe innovations in experimental techniques and instrumentation for studying all aspects of microcirculatory structure and function.
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