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Publication : Quantitative mapping of ion channel regulation by visual cycle activity in rodent photoreceptors in vivo.

First Author  Berkowitz BA Year  2009
Journal  Invest Ophthalmol Vis Sci Volume  50
Issue  4 Pages  1880-5
PubMed ID  19060264 Mgi Jnum  J:146669
Mgi Id  MGI:3838235 Doi  10.1167/iovs.08-2958
Citation  Berkowitz BA, et al. (2009) Quantitative mapping of ion channel regulation by visual cycle activity in rodent photoreceptors in vivo. Invest Ophthalmol Vis Sci 50(4):1880-5
abstractText  PURPOSE: To test the hypothesis that the extent of outer retina uptake of manganese, measured noninvasively with manganese-enhanced MRI (MEMRI), is a quantitative biomarker of photoreceptor ion channel regulation by visual cycle activity. METHODS: Four groups of animals were studied: control rats adapted to three different background light intensities, dark-adapted control mice systemically pretreated with retinylamine, and dark-adapted mice with a nonsense mutation in exon 3 of the RPE65 gene (RPE65(rd12)) with and without systemic 11-cis-retinal pretreatment. In all cases, rodents were anesthetized and studied with MEMRI 4 hours after manganese administration IP. Central retinal thickness and intraretinal ion channel regulation were measured from the MEMRI data. RESULT: No differences (P>0.05) in retinal thickness were noted within any arm of this study. In rats, manganese uptake was inversely proportional to the background light intensity in the outer retina but not in the inner retina. Specific inhibition at the level of RPE65 activity, either acutely with retinylamine or chronically in RPE65(rd12) mice, similarly reduced (P<0.05) outer retinal manganese uptake compared with that in control mice. In RPE65(rd12) mice, outer retinal manganese uptake returned to normal (P>0.05) after 11-cis retinal treatment. Inner retinal uptake was supernormal (P<0.05) in retinylamine-treated mice but normal in untreated or 11-cis treated RPE65(rd12) mice. CONCLUSIONS: The present data support measuring the extent of manganese uptake in the outer retina as an analytic noninvasive metric of visual cycle regulation of photoreceptor ion channel activity in vivo.
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