Calcium-independent phospholipase A(2), group VIA, is critical for RPE cell survival

PURPOSE: To investigate the significance of calcium-independent phospholipase A(2), group VIA (iPLA(2)-VIA), in RPE cell survival following responses to sodium iodate (SI) in cell cultures. METHODS: The human retinal pigment epithelium (RPE) cell line (ARPE-19) cells and primary mouse-RPE cultures were treated with SI to induce cell death. Cells were transfected with an iPLA(2)-VIA promoter-luciferase construct to evaluate the regulation of iPLA(2)-VIA after exposure to SI. PCR analysis, western blot analysis, and activity assays were performed to evaluate the mRNA level, protein level, and activity levels of iPLA(2)-VIA after SI exposure. Inhibitors of iPLA(2)-VIA were used to explore a potential protective role in cells exposed to SI. Primary RPE cell cultures were grown from iPLA(2)-VIA knockout mice and wild-type mice. The cultures were exposed to SI to investigate a possible increased protection against SI in iPLA(2)-VIA knockout mice compared to wild-type mice. RESULTS: The study revealed upregulation of iPLA(2)-VIA expression (promoter activity, iPLA(2)-VIA mRNA, iPLA(2)-VIA protein, and iPLA(2)-VIA protein activity) in ARPE-19 cells exposed to SI. SI-induced cell death was shown to be inhibited by iPLA(2)-VIA-specific inhibitors in ARPE-19 cell cultures. RPE cultures from iPLA(2)-VIA knockout mice were less vulnerable to SI-induced cell death compared to RPE cultures from wild-type mice. CONCLUSIONS: SI -induced RPE cell death involves iPLA(2)-VIA upregulation and activation, and amelioration of SI-induced RPE cell death can be facilitated by inhibitors of iPLA(2)-VIA. Thus, we suggest iPLA(2)-VIA as a possible pharmaceutical target to treat RPE-related retinal diseases.