Manganese-enhanced MRI of the DBA/2J mouse model of hereditary glaucoma.
OBJECTIVE
To test the hypothesis that manganese-enhanced magnetic resonance imaging (MEMRI) is a sensitive approach for measuring of age-related ocular changes in experimental pigmentary glaucoma.


METHODS
Four groups of light-adapted mice were studied using MEMRI: young (2-3 months), C57BL/6 (negative controls), and DBA/2J mice and aged (10-11 months) C57BL/6 and DBA/2J mice. In all mice, eye perimeter, optic nerve head width, iridocorneal angle, ciliary body area, and total and inner retinal thickness, and a surrogate of retinal ion regulation (intraretinal uptake of manganese) were assessed from MEMRI data and compared. Axon counts were obtained from optic nerves harvested from MEMRI-assessed eyes.


RESULTS
As the C57BL/6 and DBA/2J mice aged, differential and significant changes in ocular perimeter, retinal thickness, iridocorneal angle, ciliary body area, and optic nerve head width were readily measured from MEMRI data (P < 0.05). In C57BL/6 mice, only inner retinal thickness and perimeter were correlated. In DBA/2J mice, ocular perimeter was correlated with total and inner retinal thickness, ciliary body area, optic nerve head width, and iridocorneal angle. Comparison of young and aged mice revealed a subnormal intraretinal manganese uptake (P < 0.05) in aged DBA/2J mice, but not in aged C57BL/6 mice. Manganese uptake did not correlate with the ocular perimeter. Axon density in the optic nerve correlated with MEMRI-measured optic nerve head width (P < 0.05).


CONCLUSIONS
These studies provide a baseline of noninvasive MEMRI-detectable changes associated with age in a common animal model of hereditary glaucoma that may be useful in the longitudinal evaluation of therapeutic success.
Department of Ophthalmology and Visual Sciences, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
David J
DJ
Calkins
Philip J
PJ
Horner
Robin
R
Roberts
Marius
M
Gradianu
Bruce A
BA
Berkowitz
D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology; D002924:Ciliary Body / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005500:Follow-Up Studies; D005902:Glaucoma, Open-Angle / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008345:Manganese / Q000493:pharmacokinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009898:Optic Disk / Q000378:metabolism / Q000473:pathology; D015203:Reproducibility of Results; D012160:Retina / Q000378:metabolism / Q000473:pathology*; D012720:Severity of Illness Index; D014131:Trace Elements / Q000493:pharmacokinetics
D014131:Trace Elements; D008345:Manganese