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B. A. Berkowitz, R. Roberts, H. Luan, D. Bissig, B. V. Bui, A. J. Vingrys, M. Gradianu; Manganese-Enhanced MRI Studies of Intraretinal Dyshomeostasis. Invest. Ophthalmol. Vis. Sci. 2007;48(13):113.
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To test the hypothesis that uptake of manganese, detected with manganese-enhanced MRI (MEMRI), is a sensitive and non-toxic metric of intraretinal ion dyshomeostasis as demonstrated following suppression of retinal Na-K ATPase activity with ouabain.
To assess choroidal contribution, high resolution images were collected on 5 light adapted rats before and after Gd-DTPA injection i.v. To assess toxicity, ERGs were collected over an 8 log unit range of exposures (-6.1 to 2.2 log scot cd.s/m2) on 6 dark adapted (>12 hrs) rats before and after (4 hrs, 7 days) injection of MnCl2. Waveforms were collected (4 kHz, 0.3-1000 Hz) with corneal and scleral electrodes (Ag-AgCl) with a tail ground. Retinal layer-specific ion demand and retinal thickness were non-invasively and simultaneously measured from high resolution MEMRI data 4 hrs after MnCl2 (44 mg/kg,i.p.) injection. Two light adapted groups were studied with MEMRI: 5 control rats given phosphate buffered saline (PBS, 3 µl) intravitreally 20 hrs prior to MnCl2 injection, and 5 experimental rats given PBS+ouabain (0.55mM/3µl) intravitreally 20 hrs prior to MnCl2 injection). .
Comparing pre and post-Gd-DTPA images allowed for an estimate of choroidal thickness (65.5 + 7.6 mm (n = 5)) and a demonstration of a minimal choroidal contribution to intraretinal analysis. The ERG showed no effect on photoreceptor a-wave and post-receptor b-wave at either observation time (0 v 4 hrs or 7 days). After ouabain injection, receptor and post-receptor uptake of manganese was subnormal (P < 0.05).
Uptake of systemically administered and non-toxic dose of manganese appears to provide a powerful approach for measuring alterations in intraretinal ion homeostasis.
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