Manganese-enhanced MRI studies of alterations of intraretinal ion demand in models of ocular injury.
OBJECTIVE
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.
Berkowitz
Bruce A
BA
Department of Anatomy and Cell Biology, Wayne State University, Detroit, Michigan 48201, USA.
Roberts
Robin
R
Luan
Hongmei
H
Bissig
David
D
Bui
Bang V
BV
Gradianu
Marius
M
Calkins
David J
DJ
Vingrys
Algis J
AJ
D000818:Animals; D001813:Blood-Retinal Barrier / Q000378:metabolism; D002712:Chlorides / Q000493:pharmacokinetics / Q000633:toxicity; D002829:Choroid / Q000098:blood supply; D003287:Contrast Media; D004596:Electroretinography; D004791:Enzyme Inhibitors / Q000633:toxicity; D005260:Female; D019786:Gadolinium DTPA; D007452:Iodates / Q000633:toxicity; D008279:Magnetic Resonance Imaging / Q000379:methods* / Q000592:standards; D017895:Manganese Compounds / Q000493:pharmacokinetics; D008954:Models, Biological; D010042:Ouabain / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012160:Retina / Q000473:pathology* / Q000502:physiology; D012164:Retinal Diseases / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology
D002712:Chlorides; D003287:Contrast Media; D004791:Enzyme Inhibitors; D007452:Iodates; D017895:Manganese Compounds; D010042:Ouabain; D019786:Gadolinium DTPA; C025340:manganese chloride; C032285:sodium iodate