Manganese-Enhanced MRI of the DBA/2J Mouse Model of Hereditary Glaucoma

Abstract

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. 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. 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). 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.