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Originally published In Press as doi:10.1167/iovs.08-2205 on June 14, 2008
 (Investigative Ophthalmology and Visual Science. 2008;49:5083-5088.)
© 2008 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.08-2205
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Manganese-Enhanced MRI of the DBA/2J Mouse Model of Hereditary Glaucoma

David J. Calkins,1 Philip J. Horner,2 Robin Roberts,3 Marius Gradianu,3 and Bruce A. Berkowitz3,4

1From the Department of Ophthalmology and Visual Sciences, Vanderbilt University Medical Center, Nashville, Tennessee; the 2Department of Neurosurgery, University of Washington, Seattle, Washington; and the 3Departments of Anatomy and Cell Biology and 4Ophthalmology, Wayne State University, Detroit, Michigan.

PURPOSE. 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.




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Invest. Ophthalmol. Vis. Sci., April 1, 2009; 50(4): 1880 - 1885.
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