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V. Enzmann, L. M. Franco, D. C. Dean, R. Zulliger, H. J. Kaplan, S. Wolf; The Optokinetic Reflex (OKR) is a Sensitive Measure of Visual Behavior in the Sodium Iodate-Induced Model of RPE Damage. Invest. Ophthalmol. Vis. Sci. 2008;49(13):473.
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We have previously reported that the systemic administration of sodium iodate (NaIO3) resulted in RPE damage and abnormal electrophysiologic responses in the mouse eye. Our present study was designed to correlate the morphologic damage to the RPE caused by different doses of NaIO3 with visual behavior.
Damage to the retinal pigment epithelium (RPE) was generated with a single intravenous injection of 1% sterile sodium iodate (NaIO3), at a dose of 15, 25 and 35 mg/kg, in 4-6 week old male C57BL/6 mice. Visual function was assessed with both a cued water maze (WM) behavioral test and the optokinetic reflex (OKR) measurement at different time points post-injection (day 3, 7, 14, 21, and 28 PI). To investigate the morphologic correlation of the NaIO3 doses RPE autofluorescence in whole eye flat mounts was quantified using laser scanning microscopy and imaging software. Furthermore, H&E staining of paraffin eye sections was performed to assess changes in the outer neurosensory retinal anatomy.
Recording vision-based behavior in the cued WM test showed significant differences after injection of 35 mg/ kg and 25 mg/ kg NaIO3 beginning on day 14 PI. In contrast, 15 mg/ kg NaIO3 did not cause detectable inhibition of the water task. On the other hand, OKR measurement revealed a complete lack of the reflex after injection of 35 mg/ kg and 25 mg/ kg NaIO3 beginning on day 1 PI, with a small recovery at the latter dose from day 7 PI. The lowest dose, 15 mg/ kg NaIO3, also showed a significantly diminished, but measurable, OKR at all time points. Measurement of autofluorescence revealed focal RPE loss beginning on day 21 with 15 mg/ kg NaIO3; in contrast, large areas of RPE loss were noted on day 14 with 25 mg/ kg, and on day 7 with 35 mg/kg NaIO3. The thickness and number of nuclei in the ONL were significantly reduced in both the 35 and 25 mg/ kg groups beginning on day 7 and day 14 PI, respectively. In contrast, 15 mg/ kg did not significantly change the structure of the ONL.
Using a low concentration of NaIO3, patchy RPE loss was observed and remained stable over one month. At higher concentrations of NaIO3, widespread damage of the RPE was observed with secondary damage to the ONL of the retina. The OKR measurement was more sensitive than the cued WM test to monitor visual behavior after RPE damage. Thus, the NaIO3 model is useful to test the effectiveness of cell replacement therapy since it allows the correlation of morphologic, electrophysiologic and visual behavioral testing.
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