Conclusions
SI -induced RPE cell death involves iPLA&sub2;-VIA upregulation and activation, and amelioration of SI-induced RPE cell death can be facilitated by inhibitors of iPLA&sub2;-VIA. Thus, we suggest iPLA&sub2;-VIA as a possible pharmaceutical target to treat RPE-related retinal diseases.
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&sub2;-VIA promoter-luciferase construct to evaluate the regulation of iPLA-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&sub2;-VIA after SI exposure. Inhibitors of iPLA&sub2;-VIA were used to explore a potential protective role in cells exposed to SI. Primary RPE cell cultures were grown from iPLA&sub2;-VIA knockout mice and wild-type mice. The cultures were exposed to SI to investigate a possible increased protection against SI in iPLA&sub2;-VIA knockout mice compared to wild-type mice.
Purpose
To investigate the significance of calcium-independent phospholipase A&sub2;, group VIA (iPLA2-VIA), in RPE cell survival following responses to sodium iodate (SI) in cell cultures.
Results
The study revealed upregulation of iPLA&sub2;-VIA expression (promoter activity, iPLA&sub2;-VIA mRNA, iPLA&sub2;-VIA protein, and iPLA&sub2;-VIA protein activity) in ARPE-19 cells exposed to SI. SI-induced cell death was shown to be inhibited by iPLA&sub2;-VIA-specific inhibitors in ARPE-19 cell cultures. RPE cultures from iPLA&sub2;-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&sub2;-VIA upregulation and activation, and amelioration of SI-induced RPE cell death can be facilitated by inhibitors of iPLA&sub2;-VIA. Thus, we suggest iPLA&sub2;-VIA as a possible pharmaceutical target to treat RPE-related retinal diseases.