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Chang-Ning Liu, David Yates, Qinghai Peng, Wenhu Huang, Heather Devantier, Shirley Aguirre; Sodium Iodate Causes Photoreceptor Damage in Cynomolgus Monkeys. Invest. Ophthalmol. Vis. Sci. 2016;57(12):80.
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© ARVO (1962-2015); The Authors (2016-present)
Toxic effects of sodium iodate (NaIO3) on the retinal pigment epithelium (RPE) and secondarily on the photoreceptors have been reported. Though widely used as a model to induce retinal damage in rodents, application in large animal species has encountered species-dependent variation in toxicity. For example, NaIO3 induces outer retinal degeneration and electroretinogram (ERG) changes in sheep, while having no effect at similar dose in swine. In monkeys, administration of NaIO3 via a carotid artery affected ipsilateral RPE function, but did not affect the contralateral eye. The sub-lethal NaIO3 dosage in monkey and secondary damage to photoreceptors are unknown. The aim of the present study was to evaluate whether NaIO3 could induce retinal change functionally and morphologically in cynomolgus monkeys.
Four 4-5 year-old male and female monkeys were dosed intravenously (IV) with single or repeat doses (days 1-2) of NaIO3 at 30 mg/kg and another 2 animals were dosed with vehicle. On day 5, full-field flash ERG was recorded followed by necropsy. After 40 minutes of dark adaptation, scotopic rod responses and rod and cone maximal responses were assessed. After 10 min light adaptation, photopic flicker and cone responses were then evaluated. The eyes, harvested during necropsy, was fixed with 3% glutaraldehyde and examined microscopically and circulating retinal microRNA-183 clusters (miR-183) were measured in blood collected on days 1, 4 and 5 postdose.
There were no differences noted in scotopic oscillatory potentials between treated and control animals. A statistically significantly reduction in both scotopic and photopic b-wave signals (p <0.05) were observed, coupled with time-dependent elevations in plasma miR-183, suggesting it may serve as potential biomarkers of retinal injury. Significant morphologic changes were observed microscopically in the outer layer of the retina which correlated with the functional and clinical observations. There was no sex difference in any functional or structural endpoints.
We conclude that sub-lethal NaIO3 markedly damaged the photoreceptors both functionally and morphologically in cynomolgus monkeys at 30 mg/kg for 1-2 days.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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