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Nat Commun. 2017 May 19;8:15374. doi: 10.1038/ncomms15374.

Concerted regulation of retinal pigment epithelium basement membrane and barrier function by angiocrine factors.

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Department of Ophthalmology, Margaret Dyson Vision Research Institute, Weill Cornell Medicine, 1300 York Avenue, New York, New York 10065, USA.
Angiocrine Bioscience, Inc., 11575 Sorrento Valley Road, Suite 217, San Diego, California 92121, USA.
Department of Physiology and Biophysics, Weill Cornell Medicine, 1300 York Avenue, New York, New York 10065, USA.
Burke Medical Research Institute, 785 Mamaroneck Avenue, White Plains, New York 10605, USA.
Bioengineering Program, DeMatteis School of Engineering and Applied Science, Hofstra University, 1000 Fulton Avenue, Hempstead, New York 11549, USA.
Ansary Stem Cell Institute, Department of Medicine, Division of Regenerative Medicine, Weill Cornell Medicine, 1300 York Avenue, New York, New York 10065, USA.
Section of Epithelial and Retinal Physiology and Disease, National Eye Institute, National Institutes of Health, 31 Center Drive MSC 2510, Bethesda, Maryland 20892-2510, USA.


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.

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