title: Retinal Cell Death Caused by Sodium Iodate Involves Multiple Caspase-Dependent and Caspase-Independent Cell-Death Pathways.
abstract: 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.
authors.affiliation: Department of Ophthalmology, Inselspital, University of Bern, Bern 3010, Switzerland. jasmin.balmer@ndcn.ox.ac.uk.|Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK. jasmin.balmer@ndcn.ox.ac.uk.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Balmer
authors.affiliation: Department of Cell Biology, the University of Oklahoma Health Sciences Center, University of Oklahoma, Oklahoma City, OK 73104, USA. rahel-zulliger@ouhsc.edu.
authors.forename: Rahel
authors.initials: R
authors.lastname: Zulliger
authors.affiliation: Department of Ophthalmology, Inselspital, University of Bern, Bern 3010, Switzerland. s.roberti@gmx.net.
authors.forename: Stefano
authors.initials: S
authors.lastname: Roberti
authors.affiliation: Department of Ophthalmology, Inselspital, University of Bern, Bern 3010, Switzerland. volker.enzmann@insel.ch.|Department for Clinical Research, University of Bern, Bern 3010, Switzerland. volker.enzmann@insel.ch.
authors.forename: Volker
authors.initials: V
authors.lastname: Enzmann
mesh_terms: D000818:Animals; D017209:Apoptosis; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D007452:Iodates / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D009336:Necrosis; D012162:Retinal Degeneration / Q000209:etiology / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000378:metabolism*
chemical_list: D007452:Iodates; D020169:Caspases; C032285:sodium iodate
keywords: apoptosis; cell death; in vitro; in vivo; necrosis; photoreceptors; retinal pigment epithelium; sodium iodate