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内皮通透性途径在小鼠血视网膜屏障发育中的表达模式。

Expression patterns of endothelial permeability pathways in the development of the blood-retinal barrier in mice.

机构信息

Departments of Ophthalmology and Medical Biology, Amsterdam UMC, Ocular Angiogenesis Group, Amsterdam Cardiovascular Sciences, Cancer Center Amsterdam, University of Amsterdam, Amsterdam, The Netherlands.

Department of Medical Biology, Amsterdam UMC, Electron Microscopy Center Amsterdam, University of Amsterdam, Amsterdam, The Netherlands.

出版信息

FASEB J. 2019 Apr;33(4):5320-5333. doi: 10.1096/fj.201801499RRR. Epub 2019 Jan 30.

Abstract

Insight into the molecular and cellular processes in blood-retinal barrier (BRB) development, including the contribution of paracellular and transcellular pathways, is still incomplete but may help to understand the inverse process of BRB loss in pathologic eye conditions. In this comprehensive observational study, we describe in detail the formation of the BRB at the molecular level in physiologic conditions, using mice from postnatal day (P)3 to P25. Our data indicate that immature blood vessels already have tight junctions at P5, before the formation of a functional BRB. Expression of the endothelial cell-specific protein plasmalemma vesicle-associated protein (PLVAP), which is known to be involved in transcellular transport and associated with BRB permeability, decreased during development and was absent when a functional barrier was formed. Moreover, we show that PLVAP deficiency causes a transient delay in retinal vascular development and changes in mRNA expression levels of endothelial permeability pathway proteins.-Van der Wijk, A.-E., Wisniewska-Kruk, J., Vogels, I. M. C., van Veen, H. A., Ip, W. F., van der Wel, N. N., van Noorden, C. J. F., Schlingemann, R. O., Klaassen, I. Expression patterns of endothelial permeability pathways in the development of the blood-retinal barrier in mice.

摘要

对血视网膜屏障 (BRB) 发育中分子和细胞过程的深入了解,包括细胞旁和细胞内途径的贡献,仍然不完整,但可能有助于理解病理性眼部疾病中 BRB 丧失的相反过程。在这项全面的观察性研究中,我们详细描述了生理条件下 BRB 在分子水平上的形成,使用了从出生后第 3 天到第 25 天的小鼠。我们的数据表明,不成熟的血管在 P5 时已经具有紧密连接,而在功能性 BRB 形成之前。已知参与细胞内转运并与 BRB 通透性相关的内皮细胞特异性蛋白质膜小泡相关蛋白 (PLVAP) 的表达在发育过程中降低,并且在形成功能性屏障时消失。此外,我们表明 PLVAP 缺乏会导致视网膜血管发育短暂延迟,并改变内皮通透性途径蛋白的 mRNA 表达水平。-Van der Wijk,A.-E.,Wisniewska-Kruk,J.,Vogels,I. M. C.,van Veen,H. A.,Ip,W. F.,van der Wel,N. N.,van Noorden,C. J. F.,Schlingemann,R. O.,Klaassen,I. 内皮通透性途径蛋白在小鼠血视网膜屏障发育中的表达模式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5228/6436651/54485194d74b/fj.201801499RRRf1.jpg

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