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James M. Tsahakis, Brian J. Carlson, Wendi S. Lambert, Daniel C. Colvin, David J. Calkins; Manganese-Enhanced MRI Retinal Calcium Uptake in a Rat Model of Glaucoma. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2491.
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Increased intraocular pressure in glaucoma is associated with disrupted Ca2+ homeostasis in both the retina and optic nerve. As both a Ca2+ analogue and MRI contrast agent that shortens T1 relaxation times, Mn2+ can be used as a surrogate marker for activity-dependent signaling. Here we used Mn2+-enhanced MRI (MEMRI) to investigate changes in Ca2+ activity following short-term elevations in intraocular pressure (IOP) in a rat model of glaucoma.
We elevated IOP by injection of polystyrene microbeads into the anterior chamber of the left eye of Brown Norway rats; the right eye received an equivalent volume saline injection to serve as a control. IOP was measured for a period of either 6 or 20 days, after which each eye was imaged in vivo with a 4.7T 31-cm bore Varian DirectDrive MRI scanner 4 hours following intraperitoneal injection of MnCl2 (60 mg/kg). We compiled MEMRI T1 maps of the retina from multiple cross-sectional scans per animal.
Microbead injection elicited a consistent 25-35% elevation in IOP compared to the control eye for both the 6-day and 20-day cohorts. Mapping of T1 values showed a decrease of 8% in the overall thickness of the retina after 6 days of elevated IOP and a decrease of 18% after 20 days. These changes were reflected by increased retinal T1 values of 12-28% in the microbead-injected eye compared to the saline eye, especially in the region proximal to the optic nerve head.
Modest elevations in IOP over even a limited period (6-20 days) diminish MEMRI signals in the retina as measured by increased T1 relaxation times. Since longer T1 values indicate decreased Mn2+ uptake, our results suggest that limited elevations in IOP diminish homeostatic retinal Ca2+ activity. How this activity changes over longer periods of IOP elevation is important for understanding the contribution of Ca2+-dependent mechanisms to progression.
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