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W. Wang, J. N. Brodfuehrer, L. Zhou, D. C. Dean, M. A. McCall, H. J. Kaplan; Intravenous Injection of Sodium Iodate Causes a Central-To-Peripheral Gradient of Retinal Pigment Epithelial (RPE) and Photoreceptor Loss. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2236. doi: https://doi.org/.
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Intravenous (IV) injection of NaIO3 selectively targets and eliminates the RPE in a dose dependent manner. As a secondary consequence of RPE damage, retinal photoreceptors undergo degeneration and retinal function measured by the electroretinogram (ERG) declines. Although NaIO3 has been used previously to produce RPE damage in many species, the uniformity of its effect across the retina has not been examined. We compared the effect of NaIO3 on RPE between central and peripheral retina and correlated this with photoreceptor apoptosis. Retinal and visual function were measured using ERG and the optiokinetic response (OKR), respectively.
C57B6 (WT) mice (n = 10) were administered 25mg/kg NaIO3 IV. Visual function was assessed before NaIO3 treatment with the OKR and at 3 days and 2 and 6 weeks post-injection (PI). Both dark- and light-adapted ERGs were used to assess retinal function at 2 and 6 weeks PI. At six weeks, mice were euthanized and eyes were enucleated and fixed in 4% paraformaldehyde. The eyes were embedded in paraffin and 4µm thick sections were cut and stained either with H&E for nuclei counts or immunohistochemistry for apoptosis. The data for central and peripheral regions of the inner and outer nuclear layers were compared.
At 25 mg/kg, NaIO3 causes patchy loss of RPE and this loss is more severe in the central retina. Concomitant with RPE loss, there is increased apoptosis of photoreceptors in the central retinal, which also is reflected in a decline in the number of nuclei in the ONL. Apoptosis was not evident in the INL and there was no significant change in the number of nuclei in the INL. There was a severe reduction in the ERG of NaIO3 treated mice and in their OKR.
NaIO3 induces a central-to-peripheral gradient of RPE loss, which leads to a similar gradient of apoptosis of underlying photoreceptors.
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