Journal
STEM CELL REPORTS
Volume 10, Issue 3, Pages 1075-1087Publisher
CELL PRESS
DOI: 10.1016/j.stemcr.2018.01.017
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Funding
- NIH [EY26215]
- Empire State Stem Cell Fund through New York State Department of Health [C028504]
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With stem cell-derived retinal pigment epithelial (RPE) replacement therapies in clinical testing, establishing potency of RPE prior to transplantation is imperative. Phagocytosis of photoreceptor outer segment fragments (POS) is a key indicator of RPE functionality. Comparing RPE derived from different donor human adult RPE stem cell lines, we found that cells were either high-phagocytic or low-phagocytic despite sharing phagocytic receptors and ligands, junctional ZO-1, and lack of epithelial-mesenchymal transition. We found that low-phagocytic cells harbored F-actin stress fibers but lacked contiguous lateral circumferential F-actin and ezrin-rich microvilli of high-phagocytic cells. Rho kinase inhibition reversed the F-actin phenotype and restored phagocytic capacity to low-phagocytic RPE. Conversely, RhoA activation induced stress fiber formation and reduced phagocytic function of high-phagocytic RPE. These results demonstrate that a stress fiber-rich microfilament cytoskeleton causes phagocytic dysfunction of RPE cells. We propose F-actin assessment as a rapid, sensitive, and quantitative test to identify RPE populations lacking phagocytic capacity.
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