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(Investigative Ophthalmology and Visual Science. 2007;48:3796-3804.)
© 2007 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.06-1278
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Manganese-Enhanced MRI Studies of Alterations of Intraretinal Ion Demand in Models of Ocular Injury

Bruce A. Berkowitz,1,2 Robin Roberts,1 Hongmei Luan,1 David Bissig,1 Bang V. Bui,3 Marius Gradianu,1 David J. Calkins,4 and Algis J. Vingrys3

1From the Departments of Anatomy and Cell Biology and 2Ophthalmology, Wayne State University, Detroit, Michigan; 3Optometry and Vision Sciences, University of Melbourne, Victoria, Australia; and 4Department of Ophthalmology and Visual Sciences, Vanderbilt University, Nashville, Tennessee.

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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