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.
Calkins
David J
DJ
Department of Ophthalmology and Visual Sciences, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Horner
Philip J
PJ
Roberts
Robin
R
Gradianu
Marius
M
Berkowitz
Bruce A
BA
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