NeuroImaging Laboratory, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.
UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States Louis J. Fox Center for Vision Restoration, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.
Invest Ophthalmol Vis Sci. 2014 Apr 24;55(6):3747-57. doi: 10.1167/iovs.14-14263.
Although glaucoma treatments alter aqueous humor (AH) dynamics to lower intraocular pressure, the regulatory mechanisms of AH circulation and their contributions to the pathogenesis of ocular hypertension and glaucoma remain unclear. We hypothesized that gadolinium-enhanced magnetic resonance imaging (Gd-MRI) can visualize and assess AH dynamics upon sustained intraocular pressure elevation and pharmacologic interventions.
Gadolinium contrast agent was systemically administered to adult rats to mimic soluble AH components entering the anterior chamber (AC) via blood-aqueous barrier. Dynamic Gd-MRI was applied to examine the signal enhancement in AC and vitreous body upon microbead-induced ocular hypertension and unilateral topical applications of latanoprost, timolol maleate, and brimonidine tartrate to healthy eyes.
Gadolinium signal time courses in microbead-induced hypertensive eyes possessed faster initial gadolinium uptake and higher peak signals in AC than control eyes, reflective of reduced gadolinium clearance upon microbead occlusion. Opposite trends were observed in latanoprost- and timolol-treated eyes, indicative of their respective drug actions on increased uveoscleral outflow and reduced AH production. The slowest initial gadolinium uptake but strongest peak signals were found in AC of both brimonidine-treated and untreated fellow eyes. These findings drew attention to the systemic effects of topical hypotensive drug treatment. Gadolinium leaked into the vitreous of microbead-induced hypertensive eyes and brimonidine-treated and untreated fellow eyes, suggestive of a compromise of aqueous-vitreous or blood-ocular barrier integrity.
Gadolinium-enhanced MRI allows spatiotemporal and quantitative evaluation of altered AH dynamics and ocular tissue permeability for better understanding the physiological mechanisms of ocular hypertension and the efficacy of antiglaucoma drug treatments.
尽管青光眼治疗方法通过改变房水（aqueous humor，AH）动力学来降低眼内压，但 AH 循环的调节机制及其对眼高压和青光眼发病机制的贡献仍不清楚。我们假设钆增强磁共振成像（gadolinium-enhanced magnetic resonance imaging，Gd-MRI）可用于可视化和评估持续眼内压升高及药物干预下的 AH 动力学。
将钆造影剂系统地给予成年大鼠，以模拟可溶性 AH 成分通过血眼屏障进入前房（anterior chamber，AC）。应用动态 Gd-MRI 检查微珠诱导的眼高压以及单侧局部应用拉坦前列素、马来酸噻吗洛尔和酒石酸溴莫尼定对健康眼的 AC 和玻璃体信号增强情况。
微珠诱导的高血压眼中的钆信号时间曲线具有比对照眼更快的初始钆摄取和更高的 AC 峰值信号，反映了微珠阻塞时的钆清除减少。在拉坦前列素和噻吗洛尔治疗的眼中观察到相反的趋势，表明它们各自对增加葡萄膜巩膜外流和减少 AH 产生的药物作用。在接受和未接受溴莫尼定治疗的对侧眼中，AC 中的初始钆摄取最慢，但峰值信号最强。这些发现引起了人们对局部降压药物治疗的全身作用的关注。微珠诱导的高血压眼和溴莫尼定治疗和未治疗的对侧眼的玻璃体内均有钆漏出，提示房水-玻璃体液或血眼屏障完整性受损。
Gd-MRI 可实现对改变的 AH 动力学和眼组织通透性的时空和定量评估，从而更好地理解眼高压的生理机制和抗青光眼药物治疗的效果。
