Abstract
Calcium-independent phospholipase A 2, group VIA (iPLA 2-VIA) is involved in cell proliferation. This study aimed to evaluate the role of iPLA 2-VIA in retinal pigment epithelium (RPE) cell proliferation and in retinal diseases involving RPE proliferation. A human RPE cell line (ARPE-19) was used to explore this role in vitro. Proliferating ARPE-19 cells had increased expression and activity of iPLA 2-VIA. iPLA 2-VIA was found in the nuclei of proliferating ARPE-19 cells, whereas in confluent ARPE-19 cells, with limited proliferation, iPLA 2-VIA was primarily found in the cytosol. Inhibition of iPLA 2-VIA decreased the rate of proliferation, whereas over expression of iPLA 2-VIA increased the rate of proliferation. Using an experimental porcine model of RPE proliferation we demonstrated significant nuclear upregulation of iPLA 2-VIA in proliferating RPE cells in vivo. We furthermore evaluated the expression of iPLA 2-VIA in proliferative vitreoretinopathy (PVR). PVR membranes revealed nuclear expression of iPLA 2-VIA in the RPE cells which had migrated and participated in the formation of the membranes. Overall, the present results point to an important role of iPLA 2-VIA in the regulation of RPE proliferation suggesting that iPLA 2-VIA may be considered as a possible pharmaceutical target in retinal diseases involving RPE proliferation and migration.
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