Small Molecule Mediated Proliferation of Primary Retinal Pigment Epithelial Cells

Retinal pigment epithelial (RPE) cells form a monolayer adjacent to the retina and play a critical role in the visual light cycle. Degeneration of RPE cells results in retinal disorders such as age-related macular degeneration. Cell transplant strategies have potential therapeutic value for such dis...

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Bibliographic Details
Published in:ACS chemical biology 2013-07, Vol.8 (7), p.1407-1411
Main Authors: Swoboda, Jonathan G, Elliott, Jimmy, Deshmukh, Vishal, de Lichtervelde, Lorenzo, Shen, Weijun, Tremblay, Matthew S, Peters, Eric C, Cho, Charles Y, Lu, Bin, Girman, Sergej, Wang, Shaomei, Schultz, Peter G
Format: Article
Language:English
Subjects:
Animals
Biotin - analogs & derivatives
Biotin - chemistry
Biotin - pharmacology
Cell Proliferation - drug effects
Cells, Cultured
Dose-Response Relationship, Drug
Epithelial Cells - cytology
Epithelial Cells - drug effects
Fetal Stem Cells
Fluorescent Antibody Technique
Humans
Molecular Structure
Phenylurea Compounds - chemistry
Phenylurea Compounds - pharmacology
Pyrimidines - chemistry
Pyrimidines - pharmacology
Rats
Retina - cytology
Retina - drug effects
Retinal Degeneration - drug therapy
Small Molecule Libraries - pharmacology
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Summary:Retinal pigment epithelial (RPE) cells form a monolayer adjacent to the retina and play a critical role in the visual light cycle. Degeneration of RPE cells results in retinal disorders such as age-related macular degeneration. Cell transplant strategies have potential therapeutic value for such disorders; however, risks associated with an inadequate supply of donor cells limit their therapeutic success. The identification of factors that proliferate RPE cells ex vivo could provide a renewable source of cells for transplantation. Here, we report that a small molecule (WS3) can reversibly proliferate primary RPE cells isolated from fetal and adult human donors. Following withdrawal of WS3, RPE cells differentiate into a functional monolayer, as exhibited by their expression of mature RPE genes and phagocytosis of photoreceptor outer segments. Furthermore, chemically expanded RPE cells preserve vision when transplanted into dystrophic Royal College of Surgeons (RCS) rats, a well-established model of retinal degeneration.
ISSN:1554-8929
1554-8937
DOI:10.1021/cb4001712