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Manganese-enhanced MRI studies of alterations of intraretinal ion demand in models of ocular injury.

Berkowitz BA, Roberts R, Luan H, Bissig D, Bui BV, Gradianu M, Calkins DJ, Vingrys AJ
Invest Ophthalmol Vis Sci. 2007 48 (8): 3796-804

PMID: 17652754 · PMCID: PMC2041849 · DOI:10.1167/iovs.06-1278

PURPOSE - To provide proof-of-concept that the extent of intraretinal manganese uptake after systemic MnCl(2) 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 MnCl(2). 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 MnCl(2) 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 MnCl(2) 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 MnCl(2) 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.

MeSH Terms (19)

Animals Blood-Retinal Barrier Chlorides Choroid Contrast Media Electroretinography Enzyme Inhibitors Female Gadolinium DTPA Iodates Magnetic Resonance Imaging Manganese Compounds Models, Biological Ouabain Rats Rats, Sprague-Dawley Reproducibility of Results Retina Retinal Diseases

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