Direct effect of sodium iodate on neurosensory retina.
OBJECTIVE
To systematically characterize the effects of NaIO3 on retinal morphology and function.


METHODS
NaIO3 at 10, 20, or 30 mg/kg was administered by retro-orbital injection into adult C57BL/6J mice. Phenotypic and functional changes of the retina were assessed at 1, 3, 5, and 8 days postinjection by fundus imaging, optical coherence tomography (OCT), ERG, and histology. Direct NaIO3 cytotoxicity on ARPE-19 and 661W cells was quantified using lactate dehydrogenase (LDH) apoptosis assay. Effect of NaIO3 on RPE and photoreceptor gene expression was assessed in vitro and in vivo by quantitative PCR.


RESULTS
While little to no change was observed in the 10 mg/kg NaIO3-injected group, significant retinal anomalies, such as RPE atrophy and retinal thinning, were observed in both 20 and 30 mg/kg NaIO3-injected groups. Gene expression analysis showed rapid downregulation of RPE-specific genes, increase in heme oxygenase 1 expression, and induction of the ratio of Bax to Bcl-2. Electroretinographic response loss and photoreceptor gene repression preceded gross morphological changes. High NaIO3 toxicity on 661W cells was observed in vitro along with reactive oxygen species (ROS) induction. NaIO3 treatment also disrupted oxidative stress, phototransduction, and apoptosis gene expression in 661W cells. Exposure of ARPE-19 cells to NaIO3 increased expression of neurotrophins and protected photoreceptors from direct NaIO3 cytotoxicity.


CONCLUSIONS
Systematic characterization of changes associated with NaIO3 injection revealed a large variability in the severity of toxicity induced. Treatment with >20 mg/kg NaIO3 induced visual dysfunction associated with rapid suppression of phototransduction genes and induced oxidative stress in photoreceptors. These results suggest that NaIO3 can directly alter photoreceptor function and survival.
Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts.
Jinmei
J
Wang
Jared
J
Iacovelli
Carrie
C
Spencer
Magali
M
Saint-Geniez
D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D007452:Iodates / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D010857:Pigment Epithelium of Eye / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012162:Retinal Degeneration / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D041623:Tomography, Optical Coherence / Q000379:methods
D007452:Iodates; D017382:Reactive Oxygen Species; C032285:sodium iodate
cytotoxicity; oxidative stress; photoreceptor; retinal degeneration; sodium iodate