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M. Kolko, E. C. Andersen, A. Kehler, B. S. Westlund, M. H. Nissen; Inhibition of Calcium-Independent Phospholipase A2 Prevents Retinal Pigment Epithelium Cell Death. Invest. Ophthalmol. Vis. Sci. 2010;51(13):487.
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© ARVO (1962-2015); The Authors (2016-present)
The causal mechanisms of retinal pigment epithelium (RPE) cell death remain intriguing. We have previously identified calcium-independent phospholipase A2 (iPLA2-VIA) in the RPE cells and shown a role of iPLA2-VIA in RPE proliferation. Since the proliferative phenotype of RPE is only seen during pathological conditions in which both proliferation and cell death takes place, the present study elucidates a potential role of iPLA2-VIA in RPE cell death.
ARPE-19 cells and primary mouse-RPE cultures were treated with sodium-iodate (SI) to induce cell death. Cells were transfected with an iPLA2-VIA promoter-luciferase construct to evaluate the regulation of iPLA2-VIA after exposure to SI. Activity assays and western blot analysis were performed to evaluate the protein level and activity levels of iPLA2-VIA after SI-exposure. Inhibitors of iPLA2-VIA were used to explore a potential protective role in cells exposed to SI. Primary RPE cell cultures were grown from iPLA2-VIA knockout mice and wild type mice, respectively. The cultures were exposed to SI to investigate a possible increased protection against SI in iPLA2-VIA KO mice compared to wild type mice.
The present study revealed an upregulation of iPLA2-VIA promoter activity, iPLA2-VIA protein as well as iPLA2-VIA protein activity in ARPE-19 cells exposed o SI. SI-induced cell death could be ameliorated by iPLA2-VIA specific inhibitors in both APRE-19 cells and in primary mice RPE cultures. RPE cultures from iPLA2-VIA knockout mice were less vulnerable to SI-induced cell death compared to RPE cultures from wild type mice.
SI -induced RPE cell death involves iPLA2-VIA upregulation and activation and inhibition of SI-induced RPE cell death can be ameliorated by inhibitors of iPLA2-VIA. Hence, the present study reveals a role of iPLA2-VIA in RPE cell death, and it is tempting to suggest iPLA2-VIA as a possible pharmaceutical target in retinal diseases.
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