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B. A. Berkowitz, R. Roberts, D. Bissig; Quantitative Mapping of Ion Channel Regulation by Visual Cycle Activity in Rodent Photoreceptors in vivo. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2999.
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© ARVO (1962-2015); The Authors (2016-present)
To test the hypothesis that the extent of outer retina uptake of manganese is a quantitative biomarker of photoreceptor ion channel regulation by visual cycle activity.
The following groups were studied: control Sprague Dawley rats (204 - 276 g) adapted to three different background light intensities (1.8 + 0.7 Lux , 51.3 + 11.7 Lux, 250.2 + 19.3 Lux), dark-adapted control mice (C57BL/6, WT) without any treatment, WT mice systemically pre-treated with retinylamine (which produces a long-lasting but impermanent inhibition of 11-cis-retinal production without associated retinal degeneration), and dark-adapted mice with a nonsense mutation in exon 3 of the RPE65 gene (RPE65rd12, on a C57BL/6 background) with and without systemic 11-cis-retinal pre-treatment. In all cases, rodents were anesthetized and examined with MEMRI after i.p. manganese administration. MEMRI data were analyzed for central retinal thickness and intraretinal ion channel regulation as previously described.
No differences (P > 0.05) in retinal thickness were noted within any arm of this study. In rats, manganese uptake was proportional (r = -0.99, P = 0.034) to the log10 of the background light intensity for outer retina but not for inner retina. Specific inhibition at the level of RPE65 activity, either acutely with retinylamine or chronically in RPE65rd12 mice, reduced (P < 0.05) outer retinal manganese uptake compared with that in WT mice. In RPE65rd12 mice, outer retinal manganese uptake returned to normal (P > 0.05) following 11-cis retinal treatment. Inner retinal uptake was normal in untreated or 11-cis treated RPE65rd12 mice but supernormal (P < 0.05) in retinylamine treated mice, perhaps as an acute response to the retinylamine.
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