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Jinmei Wang, Jared Iacovelli, Carrie Spencer, Magali Saint-Geniez; Sodium Iodate Induces Rapid Neuroretinal Dysfunction Prior To RPE Changes. Invest. Ophthalmol. Vis. Sci. 2013;54(15):723.
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To systemically characterize the effects of NaIO3 on retinal morphology and function.
10, 20 or 30 mg/kg NaIO3 and saline solution was administered by retro-orbital injection to adult C57BL/6 mice. Phenotypic changes of the outer retina were assessed at 1, 3, 5 and 8 days post injection by fundus imaging, optical coherence tomography (OCT), and H&E staining. Longitudinal study of visual behavior was performed by electroretinography (ERG). Expression levels of specific visual cycle genes, apoptosis, and oxidative stress genes together with visual phototransduction pathway genes were measured by quantitative RT-PCR.
Very few functional and morphological changes were observed in the 10mg/kg group and ERG recordings remained normal up to 8 days post-injection. Regional RPE dystrophy followed by progressive RPE loss was observed through fundus. Significant outer nuclear layer thinning measured by OCT and histology was also observed at later time-points. However, retinal dysfunction measured by ERG was detected before any gross morphological changes. Dramatic decrease of b-wave was detected as early as day 1 followed by loss of the a-wave by day 3-5. RPE gene expression analysis showed rapid loss of the visual cycle marker RPE65, increased in heme oxygenase 1 expression and significant induction of the Bax/Bcl-2 ratio indicating RPE dysfunction and activation of apoptotic pathways. Interestingly, multiple photoreceptor genes involved in photo-transduction such as opsin and phosphodiesterase 6B were also rapidly repressed.
Systematic characterization of retinal changes associated with NaIO3 injection revealed a large variability in the severity of the retinal toxicity induced. Treatment with 20mg/kg NaIO3 induced rapid ERG changes while the RPE and neuroretina were morphological normal. Visual dysfunction appears to be associated with significantly rapid suppression of phototransduction required genes in photoreceptors. These results suggest that NaIO3 is not only toxic to RPE but can directly alter photoreceptor function.
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