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Bruce A. Berkowitz, Robin Roberts, Hongmei Luan, David Bissig, Bang V. Bui, Marius Gradianu, David J. Calkins, Algis J. Vingrys; Manganese-Enhanced MRI Studies of Alterations of Intraretinal Ion Demand in Models of Ocular Injury. Invest. Ophthalmol. Vis. Sci. 2007;48(8):3796-3804. doi: 10.1167/iovs.06-1278.
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purpose. To provide proof-of-concept that the extent of intraretinal manganese uptake after systemic MnCl2 injection, detected with manganese-enhanced MRI (MEMRI), assesses alterations in intraretinal ion demand in models of ocular insult.
methods. In Sprague–Dawley rats, retinal ion demand and thickness were measured from MEMRI data collected before, 4 hours after, or 1, 3, and 7 days after intraperitoneal injection of MnCl2. Choroidal contribution or blood-retinal barrier permeability surface area product (BRB PS′) was determined using MRI after Gd-DTPA injection. Ocular injury was evaluated 24 hours after intravitreal injection of phosphate-buffered saline (PBS, vehicle) or PBS + ouabain, or after intraperitoneal injection of sodium iodate. Manganese retinal toxicity was assessed by comparing full-field, white-flash electroretinographic (ERG) data obtained before and after systemic MnCl2 administration. Rat choroidal thickness was measured from cross-sections prepared from paraformaldehyde-perfused adult rats.
results. Comparing pre– and post–Gd-DTPA images demonstrated minimal choroidal contribution to intraretinal analysis. Intraretinal signal intensity returned to baseline by 7 days after MnCl2 injection. After ouabain injection, receptor and postreceptor uptake of manganese were subnormal (P < 0.05). After sodium iodate exposure, intraretinal manganese uptake was supernormal (P < 0.05) and did not increase with increasing BRB PS′. ERG data did not show any effect of MnCl2 on photoreceptor a-wave and postreceptor b-wave relative to baseline at either observation time.
conclusions. MEMRI measurements of uptake of systemically administered and nontoxic doses of manganese appear to be a powerful approach for measuring alteration in intraretinal ion demand in models of ocular injury.
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