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.