Ionic dysregulatory phenotyping of Pathologic retinal thinning with manganese-enhanced MRI
Ionic dysregulatory phenotyping of Pathologic retinal thinning with manganese-enhanced MRI
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DOI：
10.1167/iovs.08-1720
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发表时间：
2008-07-01
影响因子：
4.4
通讯作者：
Roberts, Robin
中科院分区：
文献类型：
--
作者：
Berkowitz, Bruce A.;Gradianu, Marius;Roberts, Robin
目的。检验锰增强 MRI (MEMRI) 为病理性视网膜变薄中重要的视网膜离子失调表型提供灵敏且稳健的测量的假设。方法。腹腔注射 MnCl2 后 4 小时，从过夜暗适应雄性对照 Sprague - Dawley 和白化皇家外科医生学院大鼠之前（出生后发育阶段 [P]17）和光感受器变性期间（P36 和 P57）收集高分辨率 MEMRI 数据。在单独的实验中，对照大鼠，无论是否进行重复低氧预处理，均接受高 IOP (100 mm Hg) 60 分钟，然后进行 24 小时或 7 天的再灌注（例如，缺血/再灌注）。根据 MEMRI 数据测量中央视网膜厚度和视网膜内离子活性。还进行了组织学检查以确认视网膜损伤。 结果。在两种不同的神经退行性模型中，MEMRI 首次揭示了病理性视网膜变薄之前和期间视网膜内离子调节变化（P < 0.05）的证据，但没有（ P > 0.05）发育性视网膜变薄的证据。神经保护性重复缺氧预处理方案显着改变了这种表型。结论。 MEMRI 和无毒全身剂量的 MnCl2 提供了一种客观、非侵入性的离子失调表型测量方法，这似乎有助于改善一系列神经退行性疾病及其治疗的早期诊断和治疗预后。
PURPOSE. To test the hypothesis that manganese-enhanced MRI ( MEMRI) provides a sensitive and robust measure of an important retinal ionic dysregulatory phenotype in pathologic retinal thinning.METHODS. Four hours after intraperitoneal MnCl2 injection, high-resolution MEMRI data were collected from overnight dark-adapted male control Sprague - Dawley and albino Royal College of Surgeons rats before ( at development stage postnatal day [ P] 17) and during photoreceptor degeneration ( P36 and P57). In separate experiments, control rats, with and without repetitive hypoxic preconditioning, were subjected to high IOP ( 100 mm Hg) for 60 minutes followed by 24 hours or 7 days of reperfusion ( e. g., ischemia/ reperfusion). Central retinal thickness and intraretinal ion activity were measured from the MEMRI data. Histology examination was also performed to confirm retinal damage.RESULTS. In two different neurodegenerative models, MEMRI revealed first-time evidence for changes ( P < 0.05) in intraretinal ion regulation before and during pathologic, but not ( P > 0.05) developmental, retinal thinning. This phenotype was significantly altered by a neuroprotective repetitive hypoxic preconditioning protocol.CONCLUSIONS. MEMRI and a nontoxic systemic dose of MnCl2 provided an objective, noninvasive measure of an ionic deregulatory phenotype that appears useful for improved early diagnosis and treatment prognosis in a range of neurodegenerative diseases and their treatment.