Retinal Cell Death Caused by Sodium Iodate Involves Multiple Caspase-Dependent and Caspase-Independent Cell-Death Pathways

International Journal of Molecular Sciences

Jasmin Balmer²  Rahel Zulliger¹  Stefano Roberti²  Volker Enzmann² 

[1] Department of Cell Biology, the University of Oklahoma Health Sciences Center, University of Oklahoma, Oklahoma City, OK 73104, USA; E-Mail:;Department of Ophthalmology, Inselspital, University of Bern, Bern 3010, Switzerland; E-Mails:

关键词: sodium iodate;    cell death;    retinal pigment epithelium;    photoreceptors;    apoptosis;    necrosis;    in vivo;    in vitro;   

DOI  :  10.3390/ijms160715086

来源: mdpi

【 摘 要 】

Herein, we have investigated retinal cell-death pathways in response to the retina toxin sodium iodate (NaIO₃) both in vivo and in vitro. C57/BL6 mice were treated with a single intravenous injection of NaIO₃ (35 mg/kg). Morphological changes in the retina post NaIO₃ injection in comparison to untreated controls were assessed using electron microscopy. Cell death was determined by TdT-mediated dUTP-biotin nick end labeling (TUNEL) staining. The activation of caspases and calpain was measured using immunohistochemistry. Additionally, cytotoxicity and apoptosis in retinal pigment epithelial (RPE) cells, primary retinal cells, and the cone photoreceptor (PRC) cell line 661W were assessed in vitro after NaIO₃ treatment using the ApoToxGlo™ assay. The 7-AAD/Annexin-V staining was performed and necrostatin (Nec-1) was administered to the NaIO₃-treated cells to confirm the results. In vivo, degenerating RPE cells displayed a rounded shape and retracted microvilli, whereas PRCs featured apoptotic nuclei. Caspase and calpain activity was significantly upregulated in retinal sections and protein samples from NaIO₃-treated animals. In vitro, NaIO₃ induced necrosis in RPE cells and apoptosis in PRCs. Furthermore, Nec-1 significantly decreased NaIO₃-induced RPE cell death, but had no rescue effect on treated PRCs. In summary, several different cell-death pathways are activated in retinal cells as a result of NaIO₃.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.