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

TitleConcerted regulation of retinal pigment epithelium basement membrane and barrier function by angiocrine factors.
Publication TypeJournal Article
Year of Publication2017
AuthorsBenedicto 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
JournalNat Commun
Date Published2017 05 19
KeywordsAnimals, Basement Membrane, Biotinylation, Blood-Retinal Barrier, Bruch Membrane, Cell Adhesion, Cell Survival, Cells, Cultured, Choroid, Coculture Techniques, Electroretinography, Extracellular Matrix, Female, Integrins, Male, Mice, Mice, Inbred C57BL, Microscopy, Electron, Scanning, Permeability, Protein-Lysine 6-Oxidase, Retinal Pigment Epithelium, RNA, Messenger, Sequence Analysis, RNA, Tight Junctions

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.

Alternate JournalNat Commun
PubMed ID28524846
PubMed Central IDPMC5454459
Grant ListR01 EY008538 / EY / NEI NIH HHS / United States
R01 GM034107 / GM / NIGMS NIH HHS / United States