Concerted regulation of retinal pigment epithelium basement membrane and barrier function by angiocrine factors.
Concerted regulation of retinal pigment epithelium basement membrane and barrier function by angiocrine factors.
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DOI：
10.1038/ncomms15374
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发表时间：
2017-05-19
影响因子：
16.6
通讯作者：
Rodriguez-Boulan E
中科院分区：
文献类型：
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作者：
Benedicto I;Lehmann GL;Ginsberg M;Nolan DJ;Bareja R;Elemento O;Salfati Z;Alam NM;Prusky GT;Llanos P;Rabbany SY;Maminishkis A;Miller SS;Rafii S;Rodriguez-Boulan E
外血视网膜屏障是通过视网膜色素上皮（RPE）、有孔脉络膜内皮细胞（EC）和布鲁赫膜（位于两种细胞类型之间的高度组织化基底膜）的协调终末成熟建立的。在这里，我们研究脉络膜内皮细胞的贡献，这一过程中，通过比较它们的基因表达谱之前（P5）和之后（P30）的关键出生后时期，当小鼠获得成熟的视觉功能。转录组分析表明，细胞外基质相关基因的表达在此期间发生了显着变化。共培养实验支持一种新的调节途径的存在：EC分泌重塑RPE基底膜的因子，并且整合素受体感知这些变化，触发Rho GT3信号，其调节RPE紧密连接并增强RPE屏障功能。我们预计我们的结果将产生脉络膜EC在RPE生理学和疾病中的其他作用的搜索。外血视网膜屏障的建立是视网膜发育的标志，但脉络膜内皮细胞（EC）的贡献尚不清楚。在这里，作者表明在发育中的小鼠视网膜中，EC重塑基底膜并导致视网膜上皮细胞的屏障功能增强。
The outer blood-retina barrier is established through the coordinated terminal maturation of the retinal pigment epithelium (RPE), fenestrated choroid endothelial cells (ECs) and Bruch's membrane, a highly organized basement membrane that lies between both cell types. Here we study the contribution of choroid ECs to this process by comparing their gene expression profile before (P5) and after (P30) the critical postnatal period when mice acquire mature visual function. Transcriptome analyses show that expression of extracellular matrix-related genes changes dramatically over this period. Co-culture experiments support the existence of a novel regulatory pathway: ECs secrete factors that remodel RPE basement membrane, and integrin receptors sense these changes triggering Rho GTPase signals that modulate RPE tight junctions and enhance RPE barrier function. We anticipate our results will spawn a search for additional roles of choroid ECs in RPE physiology and disease. Establishment of the outer blood-retina barrier is a hallmark of retinal development but the contribution of choroid endothelial cells (ECs) is not known. Here the authors show in the developing mouse retina that ECs remodel the basement membrane and lead to enhanced barrier function of retinal epithelial cells.