Age-related changes in eye morphology and aqueous humor dynamics in DBA/2J mice using contrast-enhanced ocular MRI

Abstract

PurposeHere, we are testing the hypothesis that dynamic contrast enhanced MRI (DCE-MRI) is a useful approach for non-invasively evaluating age-related changes in aqueous humor outflow and its contribution to elevated intraocular pressure in the DBA/2J model of pigmentary glaucoma. MethodsA rodent-specific 7 T MRI was used to assess eye anatomy (anterior chamber (AC) and vitreous body (VB) morphology, eye size, lens size) and aqueous humor dynamics (via intravenous administration of Gd-DTPA and Gd-BOPTA contrast agents) in C57BL/6 and DBA/2J mice at 3 and 9 months of age. ResultsGd-MRI was used to demonstrate an anterior solute pathway into the mouse AC. Topical latanoprost treatment in C57BL/6J mice reduced Gd-BOPTA accumulation in the AC. Age-related increases in AC area, AC depth and eye size were observed in DBA/2J mice compared to C57BL/6J mice. The rate of Gd-DTPA accumulation and peak Gd-DTPA intensity was lowest in 9-month old DBA/2J mice compared to 3-month old DBA/2J mice and C57BL/6J mice at both ages. Leakage of Gd-DTPA posteriorly into the VB was also observed in 9-month old DBA/2J mice. ConclusionsThese studies support the idea that age-related changes in aqueous humor outflow contribute to elevated intraocular pressure (IOP) in the DBA/2J model of pigmentary glaucoma. Gd-MRI is a valuable tool for better understanding of mechanisms and dynamics of aqueous humor circulation in normal and glaucomatous mouse eyes or following topical administration of medicines to reduce IOP.