Role of Epithelial-Mesenchymal Transition in Retinal Pigment Epithelium Dysfunction
Retinal pigment epithelial (RPE) cells maintain the health and functional integrity of both photoreceptors and the choroidal vasculature. Loss of RPE differentiation has long been known to play a critical role in numerous retinal diseases, including inherited rod-cone degenerations, inherited macula...
Saved in:
Published in | Frontiers in cell and developmental biology Vol. 8; p. 501 |
---|---|
Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Frontiers Media S.A
25.06.2020
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | Retinal pigment epithelial (RPE) cells maintain the health and functional integrity of both photoreceptors and the choroidal vasculature. Loss of RPE differentiation has long been known to play a critical role in numerous retinal diseases, including inherited rod-cone degenerations, inherited macular degeneration, age-related macular degeneration, and proliferative vitreoretinopathy. Recent studies in post-mortem eyes have found upregulation of critical epithelial-mesenchymal transition (EMT) drivers such as TGF-β, Wnt, and Hippo. As RPE cells become less differentiated, they begin to exhibit the defining characteristics of mesenchymal cells, namely, the capacity to migrate and proliferate. A number of preclinical studies, including animal and cell culture experiments, also have shown that RPE cells undergo EMT. Taken together, these data suggest that RPE cells retain the reprogramming capacity to move along a continuum between polarized epithelial cells and mesenchymal cells. We propose that movement along this continuum toward a mesenchymal phenotype be defined as
RPE Dysfunction.
Potential mechanisms include impaired tight junctions, accumulation of misfolded proteins and dysregulation of several key pathways and molecules, such as TGF-β pathway, Wnt pathway, nicotinamide, microRNA 204/211 and extracellular vesicles. This review synthesizes the evidence implicating EMT of RPE cells in post-mortem eyes, animal studies, primary RPE, iPSC-RPE and ARPE-19 cell lines. |
---|---|
Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1 Reviewed by: Anna Matynia, University of California, Los Angeles, United States; Ashish K. Solanki, Medical University of South Carolina, United States This article was submitted to Cellular Biochemistry, a section of the journal Frontiers in Cell and Developmental Biology Edited by: Glenn Prazere Lobo, Medical University of South Carolina, United States |
ISSN: | 2296-634X 2296-634X |
DOI: | 10.3389/fcell.2020.00501 |