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骨形态发生蛋白 9 缺乏引起的眼部淋巴缺陷对眼内压没有功能影响。

Eye lymphatic defects induced by bone morphogenetic protein 9 deficiency have no functional consequences on intraocular pressure.

机构信息

University of Grenoble Alpes, Inserm, CEA, IRIG-DS-BCI, 38000, Grenoble, France.

Centre des Sciences du Goût et de l'Alimentation, AgroSup Dijon, CNRS, INRAE, Université Bourgogne Franche-Comté, 21000, Dijon, France.

出版信息

Sci Rep. 2020 Sep 29;10(1):16040. doi: 10.1038/s41598-020-71877-z.

Abstract

Aqueous humor drainage is essential for the regulation of intraocular pressure (IOP), a major risk factor for glaucoma. The Schlemm's canal and the non-conventional uveoscleral pathway are known to drain aqueous humor from the eye anterior chamber. It has recently been reported that lymphatic vessels are involved in this process, and that the Schlemm's canal responds to some lymphatic regulators. We have previously shown a critical role for bone morphogenetic protein 9 (BMP9) in lymphatic vessel maturation and valve formation, with repercussions in drainage efficiency. Here, we imaged eye lymphatic vessels and analyzed the consequences of Bmp9 (Gdf2) gene invalidation. A network of lymphatic vessel hyaluronan receptor 1 (LYVE-1)-positive lymphatic vessels was observed in the corneolimbus and the conjunctiva. In contrast, LYVE-1-positive cells present in the ciliary bodies were belonging to the macrophage lineage. Although enlarged conjunctival lymphatic trunks and a reduced valve number were observed in Bmp9-KO mice, there were no morphological differences in the Schlemm's canal compared to wild type animals. Moreover, there were no functional consequences on IOP in both basal control conditions and after laser-induced ocular hypertonia. Thus, the BMP9-activated signaling pathway does not constitute a wise target for new glaucoma therapeutic strategies.

摘要

房水引流对于调节眼内压(IOP)至关重要,而眼内压是青光眼的主要危险因素之一。已知施莱姆氏管和非传统的葡萄膜巩膜途径可从前房排出眼内的房水。最近有报道称,淋巴管参与了这一过程,而且施莱姆氏管对一些淋巴调节因子有反应。我们之前的研究表明,骨形态发生蛋白 9(BMP9)在淋巴管成熟和瓣膜形成中起着关键作用,对引流效率有影响。在这里,我们对眼部淋巴管进行了成像,并分析了 Bmp9(Gdf2)基因失活的后果。在角膜缘和结膜中观察到了一个由透明质酸受体 1(LYVE-1)阳性淋巴管组成的网络。相比之下,睫状体中存在的 LYVE-1 阳性细胞属于巨噬细胞系。尽管 Bmp9-KO 小鼠的结膜淋巴管主干增大且瓣膜数量减少,但与野生型动物相比,施莱姆氏管在形态上没有差异。此外,在基础对照条件下和激光诱导的眼高压后,眼压均没有出现功能上的变化。因此,BMP9 激活的信号通路并不是新的青光眼治疗策略的明智靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1938/7524742/4fc801e5cd32/41598_2020_71877_Fig1_HTML.jpg

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