Domain-specific distribution of gap junctions defines cellular coupling to establish a vascular relay in the retina
Domain-specific distribution of gap junctions defines cellular coupling to establish a vascular relay in the retina
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DOI：
10.1002/cne.24699
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发表时间：
2019-11-01
影响因子：
2.5
通讯作者：
Sagdullaev, Botir T.
中科院分区：
文献类型：
--
作者：
Ivanova, Elena;Kovacs-Oller, Tamas;Sagdullaev, Botir T.
在视网膜中，神经元间隙连接（GJs）已经建立了多种功能。然而，血管GJs的分布和功能尚不清楚。在小鼠视网膜整个支架中，我们结合了结构免疫组织化学分析和细胞偶联的功能评估，以及gj渗透性示踪剂神经生物素，以确定三种主要血管连接蛋白的分布模式。我们发现Cx43在星形胶质细胞上以点状方式表达，围绕着所有类型的血管，并在血管树的特定区域沿内皮细胞接触呈连续的弦状结构表达。具体来说，这些cx43阳性的弦起源于最细的毛细血管，并向供血动脉延伸。由于这种结构安排促进了周细胞和内皮细胞沿相应分支的强而排他的偶联，我们将该区域称为“血管中继”。Cx40的表达主要沿着原发动脉的内皮细胞接触处，不与cx43阳性细胞串重叠。在它们的占位区，Cx43和Cx40聚集在一起紧密连接，并且在较小程度上具有粘附接触，这两者都是血视网膜屏障的关键要素。最后，Cx37点与血管树所有区域的壁细胞和内皮细胞的整个表面相关。这种血管连接蛋白的组合分析和血管传递区域的鉴定将为未来健康和疾病中神经血管信号的研究提供结构基础。
In the retina, diverse functions of neuronal gap junctions (GJs) have been established. However, the distribution and function of vascular GJs are less clear. Here in the mouse retina whole mounts, we combined structural immunohistochemical analysis and a functional assessment of cellular coupling with a GJ-permeable tracer Neurobiotin to determine distribution patterns of three major vascular connexins. We found that Cx43 was expressed in punctate fashion on astroglia, surrounding all types of blood vessels and in continuous string-like structures along endothelial cell contacts in specialized regions of the vascular tree. Specifically, these Cx43-positive strings originated at the finest capillaries and extended toward the feeding artery. As this structural arrangement promoted strong and exclusive coupling of pericytes and endothelial cells along the corresponding branch, we termed this region a "vascular relay." Cx40 expression was found predominantly along the endothelial cell contacts of the primary arteries and did not overlap with Cx43-positive strings. At their occupied territories, Cx43 and Cx40 clustered with tight junctions and, to a lesser extent, with adhesion contacts, both key elements of the blood-retina barrier. Finally, Cx37 puncta were associated with the entire surface of both mural and endothelial cells across all regions of the vascular tree. This combinatorial analysis of vascular connexins and identification of the vascular relay region will serve as a structural foundation for future studies of neurovascular signaling in health and disease.