Lysophosphatidic acid stimulates proliferation of human retinal pigment epithelial cells

Wallace B Thoreson, Birgit N Khandalavala, Robert G. Manahan, Inga A. Polyak, Janette L. Liu, David M. Chacko

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)698-702
Number of pages5
JournalCurrent Eye Research
Volume16
Issue number7
DOIs
StatePublished - Aug 14 1997

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Retinal Pigments
Epithelial Cells
Proliferative Vitreoretinopathy
Cell Proliferation
Chemotaxis
G-Protein-Coupled Receptors
Wound Healing
Gels
Lysophosphatidic Acid Receptors
lysophosphatidic acid
Culture Techniques
Phosphatidic Acids
Lysophosphatidylcholines
Fibroblast Growth Factors
Cholera Toxin
Pertussis Toxin
Thrombin
Cell Movement
Phospholipids
Collagen

Keywords

  • Cell culture
  • Cell migration
  • Cell proliferation
  • Human
  • Lysophosphatidic acid
  • Proliferative vitreoretinopathy
  • Retinal pigment epithelium (RPE)

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Lysophosphatidic acid stimulates proliferation of human retinal pigment epithelial cells. / Thoreson, Wallace B; Khandalavala, Birgit N; Manahan, Robert G.; Polyak, Inga A.; Liu, Janette L.; Chacko, David M.

In: Current Eye Research, Vol. 16, No. 7, 14.08.1997, p. 698-702.

Research output: Contribution to journalArticle

Thoreson, Wallace B ; Khandalavala, Birgit N ; Manahan, Robert G. ; Polyak, Inga A. ; Liu, Janette L. ; Chacko, David M. / Lysophosphatidic acid stimulates proliferation of human retinal pigment epithelial cells. In: Current Eye Research. 1997 ; Vol. 16, No. 7. pp. 698-702.
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AU - Khandalavala, Birgit N

AU - Manahan, Robert G.

AU - Polyak, Inga A.

AU - Liu, Janette L.

AU - Chacko, David M.

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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.

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