Schur Rebecca M, Sheng Li, Sahu Bhubanananda, Yu Guanping, Gao Songqi, Yu Xin, Maeda Akiko, Palczewski Krzysztof, Lu Zheng-Rong
Department of Biomedical Engineering School of Engineering, Case Western Reserve University, Cleveland, Ohio, United States.
Department of Ophthalmology and Visual Sciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States.
Invest Ophthalmol Vis Sci. 2015 Jul;56(8):4936-42. doi: 10.1167/iovs.15-16522.
Apply manganese-enhanced magnetic resonance imaging (MEMRI) to assess ion channel activity and structure of retinas from mice subject to light-induced retinal degeneration treated with prophylactic agents.
Abca4(-/-)Rdh8(-/-) double knockout mice with and without prophylactic retinylamine (Ret-NH2) treatment were illuminated with strong light. Manganese-enhanced MRI was used to image the retina 2 hours after intravitreous injection of MnCl2 into one eye. Contrast-enhanced MRIs of the retina and vitreous humor in each experimental group were assessed and correlated with the treatment. Findings were compared with standard structural and functional assessments of the retina by optical coherence tomography (OCT), histology, and electroretinography (ERG).
Manganese-enhanced MRI contrast in the retina was high in nonilluminated and illuminated Ret-NH2-treated mice, whereas no enhancement was evident in the retina of the light-illuminated mice without Ret-NH2 treatment (P < 0.0005). A relatively high signal enhancement was also observed in the vitreous humor of mice treated with Ret-NH2. Strong MEMRI signal enhancement in the retinas of mice treated with retinylamine was correlated with their structural integrity and function evidenced by OCT, histology, and a strong ERG light response.
Manganese-enhanced MRI has the potential to assess the response of the retina to prophylactic treatment based on the measurement of ion channel activity. This approach could be used as a complementary tool in preclinical development of new prophylactic therapies for retinopathies.
应用锰增强磁共振成像（MEMRI）评估接受预防性药物治疗的光诱导视网膜变性小鼠视网膜的离子通道活性和结构。
对有无预防性视黄胺（Ret-NH2）治疗的Abca4(-/-)Rdh8(-/-)双敲除小鼠进行强光照射。在向一只眼睛玻璃体内注射MnCl2后2小时，用锰增强MRI对视网膜进行成像。评估每个实验组视网膜和玻璃体液的对比增强MRI，并将结果与治疗情况相关联。将研究结果与通过光学相干断层扫描（OCT）、组织学和视网膜电图（ERG）对视网膜进行的标准结构和功能评估进行比较。
在未照射和照射过的Ret-NH2治疗小鼠中，视网膜的锰增强MRI对比度较高，而在未接受Ret-NH2治疗的光照射小鼠视网膜中未观察到明显增强（P < 0.0005）。在接受Ret-NH2治疗的小鼠玻璃体液中也观察到相对较高的信号增强。视黄胺治疗小鼠视网膜中强烈的MEMRI信号增强与其结构完整性和功能相关，这通过OCT、组织学和强烈的ERG光反应得以证明。
锰增强MRI有潜力基于离子通道活性的测量来评估视网膜对预防性治疗的反应。这种方法可作为视网膜病变新预防性疗法临床前开发中的一种补充工具。
