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

Ignacio Benedicto, Guillermo L. Lehmann, Michael Ginsberg, Daniel J. Nolan, Rohan Bareja, Olivier Elemento, Zelda Salfati, Nazia M. Alam, Glen T. Prusky, Pierre Llanos, Sina Y. Rabbany, Arvydas Maminishkis, Sheldon S. Miller, Shahin Rafii and Enrique Rodriguez-Boulan ()
Additional contact information
Ignacio Benedicto: Margaret Dyson Vision Research Institute, Weill Cornell Medicine
Guillermo L. Lehmann: Margaret Dyson Vision Research Institute, Weill Cornell Medicine
Michael Ginsberg: Angiocrine Bioscience, Inc.
Daniel J. Nolan: Angiocrine Bioscience, Inc.
Rohan Bareja: Weill Cornell Medicine
Olivier Elemento: Weill Cornell Medicine
Zelda Salfati: Margaret Dyson Vision Research Institute, Weill Cornell Medicine
Nazia M. Alam: Burke Medical Research Institute
Glen T. Prusky: Weill Cornell Medicine
Pierre Llanos: Bioengineering Program, DeMatteis School of Engineering and Applied Science, Hofstra University
Sina Y. Rabbany: Bioengineering Program, DeMatteis School of Engineering and Applied Science, Hofstra University
Arvydas Maminishkis: Section of Epithelial and Retinal Physiology and Disease, National Eye Institute, National Institutes of Health
Sheldon S. Miller: Section of Epithelial and Retinal Physiology and Disease, National Eye Institute, National Institutes of Health
Shahin Rafii: Ansary Stem Cell Institute, Weill Cornell Medicine
Enrique Rodriguez-Boulan: Margaret Dyson Vision Research Institute, Weill Cornell Medicine

Nature Communications, 2017, vol. 8, issue 1, 1-12

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms15374

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