Calcium-independent phospholipase A2 regulates retinal pigment epithelium proliferation and may be important in the pathogenesis of retinal diseases

Research output: Contribution to journalJournal articleResearchpeer-review

M Kolko, J F Kiilgaard, J Wang, K A Poulsen, J R Andreasen, M la Cour, M H Nissen, S Heegaard, N G Bazan, J U Prause, M Kolko, J F Kiilgaard, J Wang, K A Poulsen, J R Andreasen, M la Cour, M H Nissen, S Heegaard, N G Bazan, J U Prause

Calcium-independent phospholipase A2, group VIA (iPLA2-VIA) is involved in cell proliferation. This study aimed to evaluate the role of iPLA2-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 iPLA2-VIA. iPLA2-VIA was found in the nuclei of proliferating ARPE-19 cells, whereas in confluent ARPE-19 cells, with limited proliferation, iPLA2-VIA was primarily found in the cytosol. Inhibition of iPLA2-VIA decreased the rate of proliferation, whereas over expression of iPLA2-VIA increased the rate of proliferation. Using an experimental porcine model of RPE proliferation we demonstrated significant nuclear upregulation of iPLA2-VIA in proliferating RPE cells in vivo. We furthermore evaluated the expression of iPLA2-VIA in proliferative vitreoretinopathy (PVR). PVR membranes revealed nuclear expression of iPLA2-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 iPLA2-VIA in the regulation of RPE proliferation suggesting that iPLA2-VIA may be considered as a possible pharmaceutical target in retinal diseases involving RPE proliferation and migration.
Original languageEnglish
JournalExperimental Eye Research
Volume89
Issue number3
Pages (from-to)383-91
Number of pages9
ISSN0014-4835
DOIs
Publication statusPublished - 1 Sep 2009

Bibliographical note

Keywords: Alternative Splicing; Animals; Cell Nucleus; Cell Proliferation; Cells, Cultured; Endoplasmic Reticulum; Gene Silencing; Humans; Phospholipases A2, Calcium-Independent; RNA, Small Interfering; Retinal Pigment Epithelium; Sus scrofa; Vitreoretinopathy, Proliferative

ID: 19952403