TY - JOUR
T1 - Lysophosphatidic acid stimulates proliferation of human retinal pigment epithelial cells
AU - Thoreson, Wallace B.
AU - Khandalavala, Birgit N.
AU - Manahan, Robert G.
AU - Polyak, Inga A.
AU - Liu, Janette L.
AU - Chacko, David M.
N1 - Funding Information:
This work was supported by the Gifford Research Laboratory. The authors wish to thank the Nebraska Lions Eye Bank for providing donor eyes, Dr. Richard Hunt for advice on gel contraction assays, Mr. Ronald Ertl for advice on chemotaxis assays, and Dr. Myron Toews for helpful discussions about LPA.
PY - 1997
Y1 - 1997
N2 - Purpose. Proliferative vitreoretinopathy (PVR) can arise from an exaggerated wound-healing response by retinal pigment epithelial (RPE) cells. Lysophosphatidic acid (LPA) is a simple phospholipid, which is secreted by cells, activates G protein-coupled receptors, and appears to contribute to wound healing in other tissues. The present study examined the effects of LPA on three aspects of the behavior of cultured human RPE cells that are important in the pathogenesis of PVR: proliferation, chemotaxis, and contraction. Methods. Human RPE cells were harvested from donor eyes and cultured using standard culture techniques. Proliferation was assessed by counting cells, cell migration with a modified Boyden chamber, and contraction by seeding RPE cells in a collagen gel. Results. LPA (10 μM) induced RPE cell proliferation and weak chemotaxis, but no gel contraction. RPE cell proliferation increased in a dose-dependent manner from 0.1-100 μM LPA. Consistent with LPA actions at a receptor, an LPA analogue, lysophosphatidylcholine (LPC), was much less effective than LPA in stimulating proliferation and the proliferative response was blocked by pertussis or cholera toxin. Phosphatidic acid (PA) induced a similar proliferative response as LPA. Conclusion. These results suggest that LPA can potently stimulate RPE cell proliferation via activation of a G-protein coupled receptor. LPA, which can be released by thrombin-activated platelets and growth factor-activated fibroblasts, might, therefore, play a role in the development of PVR.
AB - Purpose. Proliferative vitreoretinopathy (PVR) can arise from an exaggerated wound-healing response by retinal pigment epithelial (RPE) cells. Lysophosphatidic acid (LPA) is a simple phospholipid, which is secreted by cells, activates G protein-coupled receptors, and appears to contribute to wound healing in other tissues. The present study examined the effects of LPA on three aspects of the behavior of cultured human RPE cells that are important in the pathogenesis of PVR: proliferation, chemotaxis, and contraction. Methods. Human RPE cells were harvested from donor eyes and cultured using standard culture techniques. Proliferation was assessed by counting cells, cell migration with a modified Boyden chamber, and contraction by seeding RPE cells in a collagen gel. Results. LPA (10 μM) induced RPE cell proliferation and weak chemotaxis, but no gel contraction. RPE cell proliferation increased in a dose-dependent manner from 0.1-100 μM LPA. Consistent with LPA actions at a receptor, an LPA analogue, lysophosphatidylcholine (LPC), was much less effective than LPA in stimulating proliferation and the proliferative response was blocked by pertussis or cholera toxin. Phosphatidic acid (PA) induced a similar proliferative response as LPA. Conclusion. These results suggest that LPA can potently stimulate RPE cell proliferation via activation of a G-protein coupled receptor. LPA, which can be released by thrombin-activated platelets and growth factor-activated fibroblasts, might, therefore, play a role in the development of PVR.
KW - Cell culture
KW - Cell migration
KW - Cell proliferation
KW - Human
KW - Lysophosphatidic acid
KW - Proliferative vitreoretinopathy
KW - Retinal pigment epithelium (RPE)
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U2 - 10.1076/ceyr.16.7.698.5056
DO - 10.1076/ceyr.16.7.698.5056
M3 - Article
C2 - 9222088
AN - SCOPUS:0030797918
SN - 0271-3683
VL - 16
SP - 698
EP - 702
JO - Current Eye Research
JF - Current Eye Research
IS - 7
ER -