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

IF 4.7 2区 医学 Q1 PATHOLOGY American Journal of Pathology Pub Date : 2024-09-25 DOI:10.1016/j.ajpath.2024.09.003
Emmanuelle Frampton, Priyanka Som, Brittany Hill, Alexander Yu, Marina Naval-Sanchez, Chistian M Nefzger, Ivar Noordstra, Emma Gordon, Lilian Schimmel
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引用次数: 0

摘要

血管性视网膜病变的特点是视网膜血管异常增生,经常导致视力受损或丧失。新生血管丛是这种疾病的一个显著病理特征,是一种高度渗漏的血管结构,会加剧继发性并发症。尽管血管丛具有重要的临床意义,但其发生机制尚未完全阐明,这给有效管理和治疗血管性视网膜病变带来了挑战。本研究探讨了 c-Src 在新生血管丛形成中的作用。虽然 c-Src 被认为是视网膜血管发育过程中血管生成的关键调节因子,但它在病理性视网膜血管生成中的具体作用仍有待全面了解。我们利用氧诱导视网膜病变模型,在 Cre 介导的血管特异性 c-Src 基因敲除小鼠和野生型小鼠体内检测新生血管丛的形成。在氧诱导视网膜病变模型中,c-Src 基因剔除小鼠的新生血管丛明显减少。这种血管丛形成的减少与细胞死亡、细胞增殖或细胞粘附的任何改变无关,而且 c-Src 的缺失不会影响血管丛周细胞的覆盖率和连接形态。这些发现强调了 c-Src 在血管性视网膜病变新生血管丛发病机制中的关键作用。了解涉及c-Src的分子机制可为开发旨在减轻视网膜病变相关并发症威胁视力的靶向疗法提供宝贵的见解。
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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.

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来源期刊
CiteScore
11.40
自引率
0.00%
发文量
178
审稿时长
30 days
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.
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