Lysophosphatidic acid stimulates proliferation of human retinal pigment epithelial cells

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.

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 cell.

LPA (10 microM) induced RPE cell proliferation and weak chemotaxis, but no gel contraction. RPE cell proliferation increased in a dose-dependent manner from 0.1-100 microM 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.

These 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.