Schlemm's canal is a unique vessel with a combination of blood vascular and lymphatic phenotypes that forms by a novel developmental process.
Schlemm's canal is a unique vessel with a combination of blood vascular and lymphatic phenotypes that forms by a novel developmental process.
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Schlemm的运河是一种独特的血管，具有通过新型发育过程形成的血管和淋巴表型的组合。
DOI：
10.1371/journal.pbio.1001912
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发表时间：
2014-07
期刊：
影响因子：
9.8
通讯作者：
John SW
中科院分区：
文献类型：
--
作者：
Kizhatil K;Ryan M;Marchant JK;Henrich S;John SW
眼睛中的引流血管通过血管发育的新混合过程产生，并且对于理解眼内液稳态和青光眼是重要的。施累姆氏管（SC）在眼生理学中起着中心作用。这些作用依赖于SC内皮细胞（SEC）的分子表型。SECs的特异性表型和SC的发展仍然不清楚。为了对SC及其起源进行现代和广泛的分析，我们开发了一种新的整体安装程序，以可视化其在周围组织中的发展。然后，我们应用遗传谱系追踪，特异性荧光报告基因，免疫荧光，高分辨率共聚焦显微镜，和三维（3D）渲染研究SC。使用这些技术，我们表明，SEC有一个独特的表型，是血液和淋巴管内皮细胞表型的混合物。通过分析出生后小鼠的眼睛逐渐到成年的整个安装，我们表明，SC发展从血管通过一个新发现的过程，我们命名为“canalogenesis”。KDR（VEGFR2），在启动血管生成的关键受体的功能抑制，表明该受体是在canalogenesis过程中所需要的。与血管生成不同，与血管发生的各个阶段相似，在血管形成之前，在导管发生期间，尖端细胞分裂并形成支链。与血管生成和血管生成不同，在管道生成期间，SEC表达Prox 1，其是淋巴管生成和淋巴表型的主调节因子。因此，SC的发展类似于血管发育程序的混合。这些进展将SC定义为具有血管和淋巴表型组合的独特血管。它们对于解剖其对眼睛健康和正常视力至关重要的功能非常重要。施累姆氏管用作来自眼前房的流体的引流管，并且与青光眼直接相关，青光眼是一种导致超过7000万人视力丧失的疾病。水状体进入耳道，然后流入相连的静脉。对于Schlemm氏管的发育及其排水功能的分子理解仍然有限。我们提供了一个详细的描述Schlemm管的发展，并在这样做发现了一个新的过程中，我们命名为血管发育“canalogenesis。”我们表明，虽然这个过程需要一个功能性的KDR受体，这也是至关重要的血管发育，施累姆氏管的内皮细胞有一个独特的杂交分子表型，表达的蛋白质是血液和淋巴管的特征。值得注意的是，Prox 1（淋巴命运的主要调节因子）和其他淋巴蛋白的表达在很大程度上局限于施累姆氏管内壁的特化细胞，当房水离开眼睛时通过施累姆氏管。因此，Prox 1和其他淋巴蛋白可能对于这些细胞的房水引流功能特化至关重要。因此，施累姆氏管是一种独特的血管，具有血管和淋巴特性的组合。
A draining vessel in the eye arises via a novel hybrid process of vascular development and is important for understanding ocular fluid homeostasis and glaucoma. Schlemm's canal (SC) plays central roles in ocular physiology. These roles depend on the molecular phenotypes of SC endothelial cells (SECs). Both the specific phenotype of SECs and development of SC remain poorly defined. To allow a modern and extensive analysis of SC and its origins, we developed a new whole-mount procedure to visualize its development in the context of surrounding tissues. We then applied genetic lineage tracing, specific-fluorescent reporter genes, immunofluorescence, high-resolution confocal microscopy, and three-dimensional (3D) rendering to study SC. Using these techniques, we show that SECs have a unique phenotype that is a blend of both blood and lymphatic endothelial cell phenotypes. By analyzing whole mounts of postnatal mouse eyes progressively to adulthood, we show that SC develops from blood vessels through a newly discovered process that we name “canalogenesis.” Functional inhibition of KDR (VEGFR2), a critical receptor in initiating angiogenesis, shows that this receptor is required during canalogenesis. Unlike angiogenesis and similar to stages of vasculogenesis, during canalogenesis tip cells divide and form branched chains prior to vessel formation. Differing from both angiogenesis and vasculogenesis, during canalogenesis SECs express Prox1, a master regulator of lymphangiogenesis and lymphatic phenotypes. Thus, SC development resembles a blend of vascular developmental programs. These advances define SC as a unique vessel with a combination of blood vascular and lymphatic phenotypes. They are important for dissecting its functions that are essential for ocular health and normal vision. Schlemm's canal serves as a drainage tube for fluid from the anterior chamber of the eye and is directly relevant to glaucoma, a disease that causes vision loss in over 70 million people. Aqueous humor enters the canal and then drains into connected veins. Molecular understanding of the development of Schlemm's canal and its drainage functions has remained limited. We provide a detailed characterization of Schlemm's canal development, and in so doing discover a novel process of vascular development that we name “canalogenesis.” We show that although the process requires a functional KDR receptor, which is also critical in blood vessel development, the endothelial cells of Schlemm's canal have a unique hybrid molecular phenotype, expressing proteins that are characteristic of both blood and lymphatic vessels. Of note, the expression of Prox1, a master regulator of lymphatic fate, and other lymphatic proteins are largely restricted to specialized cells of the inner wall of Schlemm's canal through which the aqueous humor passes as it exits the eye. Thus, Prox1 and other lymphatic proteins may be critical for the functional specialization of these cells for aqueous humor drainage. Schlemm's canal is thus a unique vessel with a combination of blood vascular and lymphatic characteristics.
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