title: Calcium-independent phospholipase A2 regulates retinal pigment epithelium proliferation and may be important in the pathogenesis of retinal diseases.
abstract: 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.
authors.affiliation: Department of Neuroscience and Pharmacology, Eye Pathology Section, University of Copenhagen, Frederik d. V's vej 11, 1st floor, 2100 Copenhagen, Denmark. mkolko@dadlnet.dk
authors.forename: M
authors.initials: M
authors.lastname: Kolko
authors.forename: J F
authors.initials: JF
authors.lastname: Kiilgaard
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: K A
authors.initials: KA
authors.lastname: Poulsen
authors.forename: J R
authors.initials: JR
authors.lastname: Andreasen
authors.forename: M
authors.initials: M
authors.lastname: la Cour
authors.forename: M H
authors.initials: MH
authors.lastname: Nissen
authors.forename: S
authors.initials: S
authors.lastname: Heegaard
authors.forename: N G
authors.initials: NG
authors.lastname: Bazan
authors.forename: J U
authors.initials: JU
authors.lastname: Prause
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D002467:Cell Nucleus / Q000201:enzymology / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000201:enzymology; D020868:Gene Silencing; D006801:Humans; D054512:Phospholipases A2, Calcium-Independent / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D055213:Retinal Pigment Epithelium / Q000166:cytology* / Q000201:enzymology / Q000473:pathology; D034421:Sus scrofa; D018630:Vitreoretinopathy, Proliferative / Q000201:enzymology* / Q000473:pathology
chemical_list: D034741:RNA, Small Interfering; D054512:Phospholipases A2, Calcium-Independent