Epitheliomesenchymal transdifferentiation of cultured RPE cells.
Retinal pigment epithelium (RPE) cells of the proliferative vitreoretinopathy (PVR) membrane take on the shape of fibroblasts and participate in fibrosis, thus deviating from the character of epithelial cells. This study was undertaken to evaluate RPE cell transdifferentiation in vitro. During the culture of porcine RPE cells, primary and 10th-passaged RPE cells were investigated for cell growth in response to transforming growth factor (TGF) beta(2), change of phenotype and amount in collagen synthesis as well as expression of alpha-smooth-muscle actin (alpha-SMA). TGF-beta(2) inhibited the proliferation of the primary cultures of RPE cells in a dose-dependent manner, while the spindle-shaped 10th-passaged RPE cells were not inhibited by TGF-beta(2). The 10th-subcultured cells did not show much difference in the quality of collagen synthesis, other than type VIII collagen which was not produced. Collagen synthesis was dose-dependently stimulated by TGF-beta(2). The stimulation by TGF-beta(2) in the 10th-passaged RPE cells was much greater than in primary RPE cells. The 10th-subcultured RPE cells produced substantial alpha-SMA compared to alpha-SMA production by primary RPE cells. These results were also observed by confocal laser microscopy. These findings indicated that RPE metaplasia resulting in a change of biological cell behavior might be a necessary predisposing step in the development of PVR.
Lee
S C
SC
Department of Ophthalmology and Institute of Vision Research, Yonsei University College of Medicine, Seoul, Korea. sunglee@yumc.yonsei.ac.kr
Kwon
O W
OW
Seong
G J
GJ
Kim
S H
SH
Ahn
J E
JE
Kay
E D
ED
D000199:Actins / Q000096:biosynthesis; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D008679:Metaplasia; D010641:Phenotype; D010857:Pigment Epithelium of Eye / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D013552:Swine; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053781:Transforming Growth Factor beta2; D018630:Vitreoretinopathy, Proliferative / Q000473:pathology
D000199:Actins; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; D003094:Collagen