Emmanuelle Frampton, Priyanka Som, Brittany Hill, Alexander Yu, Marina Naval-Sanchez, Chistian M Nefzger, Ivar Noordstra, Emma Gordon, Lilian Schimmel
{"title":"内皮细胞 c-Src 在氧诱导视网膜病变中介导新生血管丛的形成","authors":"Emmanuelle Frampton, Priyanka Som, Brittany Hill, Alexander Yu, Marina Naval-Sanchez, Chistian M Nefzger, Ivar Noordstra, Emma Gordon, Lilian Schimmel","doi":"10.1016/j.ajpath.2024.09.003","DOIUrl":null,"url":null,"abstract":"<p><p>Vascular retinopathy, characterized by abnormal blood vessel growth in the retina, frequently results in vision impairment or loss. Neovascular tufts, a distinctive pathologic feature of this condition, are highly leaky blood vessel structures, exacerbating secondary complications. Despite their clinical significance, the mechanisms underlying tuft development are not fully elucidated, posing challenges for effective management and treatment of vascular retinopathy. This study investigates the role of c-Src in neovascular tuft formation. Although c-Src has been acknowledged as a pivotal regulator in developmental angiogenesis within the retinal vasculature, its specific role in governing pathologic retinal angiogenesis remains to be fully understood. The oxygen-induced retinopathy model was used for neovascular tuft formation in both Cre-mediated vascular-specific c-Src knockout mice and wild-type littermates. High-resolution imaging and analysis of isolated retinas were conducted. c-Src depletion demonstrated a significant reduction in neovascular tufts within the oxygen-induced retinopathy model. This decrease in tuft formation was observed independently of any alterations in cell death, cell proliferation, or cell adhesion, and the absence of c-Src did not impact tuft pericyte coverage and junctional morphology. These findings underline the critical role of c-Src in the pathogenesis of neovascular tufts in vascular retinopathy. Understanding the molecular mechanisms involving c-Src may offer valuable insights for the development of targeted therapies aimed at mitigating vision-threatening complications associated with retinopathy.</p>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":null,"pages":null},"PeriodicalIF":4.7000,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Endothelial c-Src Mediates Neovascular Tuft Formation in Oxygen-Induced Retinopathy.\",\"authors\":\"Emmanuelle Frampton, Priyanka Som, Brittany Hill, Alexander Yu, Marina Naval-Sanchez, Chistian M Nefzger, Ivar Noordstra, Emma Gordon, Lilian Schimmel\",\"doi\":\"10.1016/j.ajpath.2024.09.003\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Vascular retinopathy, characterized by abnormal blood vessel growth in the retina, frequently results in vision impairment or loss. Neovascular tufts, a distinctive pathologic feature of this condition, are highly leaky blood vessel structures, exacerbating secondary complications. Despite their clinical significance, the mechanisms underlying tuft development are not fully elucidated, posing challenges for effective management and treatment of vascular retinopathy. This study investigates the role of c-Src in neovascular tuft formation. Although c-Src has been acknowledged as a pivotal regulator in developmental angiogenesis within the retinal vasculature, its specific role in governing pathologic retinal angiogenesis remains to be fully understood. The oxygen-induced retinopathy model was used for neovascular tuft formation in both Cre-mediated vascular-specific c-Src knockout mice and wild-type littermates. High-resolution imaging and analysis of isolated retinas were conducted. c-Src depletion demonstrated a significant reduction in neovascular tufts within the oxygen-induced retinopathy model. This decrease in tuft formation was observed independently of any alterations in cell death, cell proliferation, or cell adhesion, and the absence of c-Src did not impact tuft pericyte coverage and junctional morphology. These findings underline the critical role of c-Src in the pathogenesis of neovascular tufts in vascular retinopathy. Understanding the molecular mechanisms involving c-Src may offer valuable insights for the development of targeted therapies aimed at mitigating vision-threatening complications associated with retinopathy.</p>\",\"PeriodicalId\":7623,\"journal\":{\"name\":\"American Journal of Pathology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.7000,\"publicationDate\":\"2024-09-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"American Journal of Pathology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.ajpath.2024.09.003\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PATHOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"American Journal of Pathology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ajpath.2024.09.003","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PATHOLOGY","Score":null,"Total":0}
Endothelial c-Src Mediates Neovascular Tuft Formation in Oxygen-Induced Retinopathy.
Vascular retinopathy, characterized by abnormal blood vessel growth in the retina, frequently results in vision impairment or loss. Neovascular tufts, a distinctive pathologic feature of this condition, are highly leaky blood vessel structures, exacerbating secondary complications. Despite their clinical significance, the mechanisms underlying tuft development are not fully elucidated, posing challenges for effective management and treatment of vascular retinopathy. This study investigates the role of c-Src in neovascular tuft formation. Although c-Src has been acknowledged as a pivotal regulator in developmental angiogenesis within the retinal vasculature, its specific role in governing pathologic retinal angiogenesis remains to be fully understood. The oxygen-induced retinopathy model was used for neovascular tuft formation in both Cre-mediated vascular-specific c-Src knockout mice and wild-type littermates. High-resolution imaging and analysis of isolated retinas were conducted. c-Src depletion demonstrated a significant reduction in neovascular tufts within the oxygen-induced retinopathy model. This decrease in tuft formation was observed independently of any alterations in cell death, cell proliferation, or cell adhesion, and the absence of c-Src did not impact tuft pericyte coverage and junctional morphology. These findings underline the critical role of c-Src in the pathogenesis of neovascular tufts in vascular retinopathy. Understanding the molecular mechanisms involving c-Src may offer valuable insights for the development of targeted therapies aimed at mitigating vision-threatening complications associated with retinopathy.
期刊介绍:
The American Journal of Pathology, official journal of the American Society for Investigative Pathology, published by Elsevier, Inc., seeks high-quality original research reports, reviews, and commentaries related to the molecular and cellular basis of disease. The editors will consider basic, translational, and clinical investigations that directly address mechanisms of pathogenesis or provide a foundation for future mechanistic inquiries. Examples of such foundational investigations include data mining, identification of biomarkers, molecular pathology, and discovery research. Foundational studies that incorporate deep learning and artificial intelligence are also welcome. High priority is given to studies of human disease and relevant experimental models using molecular, cellular, and organismal approaches.