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

Nature Communications
Ignacio BenedictoEnrique Rodriguez-Boulan

Abstract

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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Citations

Jul 28, 2018·Advanced Healthcare Materials·Jia-Wei YangGuan-Yu Chen
Mar 21, 2020·The Journal of Experimental Medicine·Guillermo L LehmannIgnacio Benedicto
Sep 8, 2018·Scientific Reports·Shemin ZengRobert F Mullins
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Aug 9, 2020·Stem Cells Translational Medicine·Ali E GhareebDavid H Steel
Feb 13, 2020·Investigative Ophthalmology & Visual Science·Emil CarlssonLuminita Paraoan
Sep 14, 2019·Current Opinion in Cell Biology·Paulo S Caceres, Enrique Rodriguez-Boulan
Jan 15, 2021·Scientific Reports·Taina ViheriäläTanja Ilmarinen
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Jul 20, 2021·Progress in Retinal and Eye Research·J BrinksC J F Boon
Aug 20, 2021·Frontiers in Medicine·Michael StürzlElisabeth Naschberger

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Datasets Mentioned

BETA
GSE95835

Methods Mentioned

BETA
flow cytometry
RNAseq
atomic force microscopy
electron microscopy
GTPases
GTPase
PCR

Software Mentioned

ImageJ
R
DAVID
CuffLinks
Zen ( Zeiss )
GSEA
Igor Pro
FastQC
TopHat
Asylum

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