Oxidative Stress and Light-Evoked Responses of the Posterior Segment in a Mouse Model of Diabetic Retinopathy
Oxidative Stress and Light-Evoked Responses of the Posterior Segment in a Mouse Model of Diabetic Retinopathy
复制标题
DOI：
10.1167/iovs.14-15687
复制
发表时间：
2015-01-01
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.;Grady, Edmund Michael;Roberts, Robin
目的。为了验证糖尿病视网膜病变小鼠模型中的假设，氧化应激与光诱发的脉络膜厚度和视网膜下空间（SRS）扩张受损有关。我们研究了有和没有给锰的非糖尿病小鼠（野生型，wt），缺乏棒光传导（导转导α敲除；GNAT1(-/-)）的非糖尿病小鼠，以及糖尿病小鼠（未经治疗或用抗氧化剂a-硫辛酸[LPA]治疗）。磁共振成像（MRI）测量光诱发的视网膜88% ~ 100%深度（即SRS层）脉络膜厚度和表观扩散系数（ADC）的增加。各组间脉络膜厚度相近（P < 0.05），且随光照增加而显著升高（P < 0.05）；两组的扩张均低于正常水平（P < 0.05）。SRS层的表观扩散系数值随时间的增加而显著增加（P < 0.05），且与Mn2+的存在无关。在GNAT1（-/-）和糖尿病小鼠中，SRS部位的ADC在光刺激下没有增加（P < 0.05）。在糖尿病小鼠中，lpa明显恢复了SRS ADC的光依赖性升高（P < 0.05）。视扩散系数MRI是一种灵敏的评估小鼠体内脉络膜厚度及其光诱发扩张和SRS层光导依赖性变化的方法。由于ADC MRI利用内源性对比机制，其翻译潜力是有希望的；它也可以与锰增强MRI （MEMRI）配合进行。我们的数据支持糖尿病相关氧化应激与棒状动脉病理生理之间的联系，而不是脉络膜病理生理。
PURPOSE. To test the hypothesis that in a mouse model of diabetic retinopathy, oxidative stress is linked with impaired light-evoked expansion of choroidal thickness and subretinal space (SRS).METHODS. We examined nondiabetic mice (wild-type, wt) with and without administration of manganese, nondiabetic mice deficient in rod phototransduction (transducin alpha knockout; GNAT1(-/-)), and diabetic mice (untreated or treated with the antioxidant a-lipoic acid [LPA]). Magnetic resonance imaging (MRI) was used to measure light-evoked increases in choroidal thickness and the apparent diffusion coefficient (ADC) at 88% to 100% depth into the retina (i.e., the SRS layer).RESULTS. Choroidal thickness values were similar (P > 0.05) between all untreated nondiabetic dark-adapted groups and increased significantly (P < 0.05) with light; this expansion was subnormal (P < 0.05) in both diabetic groups. Apparent diffusion coefficient values in the SRS layer robustly increased (P < 0.05) in a light duration-dependent manner, and this effect was independent of the presence of Mn2+. The light-stimulated increase in ADC at the location of the SRS was absent in GNAT1(-/-) and diabetic mice (P > 0.05). In diabetic mice, the light-dependent increase in SRS ADC was significantly (P < 0.05) restored with LPA.CONCLUSIONS. Apparent diffusion coefficient MRI is a sensitive method for evaluating choroid thickness and its light-evoked expansion together with phototransduction-dependent changes in the SRS layer in mice in vivo. Because ADC MRI exploits an endogenous contrast mechanism, its translational potential is promising; it can also be performed in concert with manganese-enhanced MRI (MEMRI). Our data support a link between diabetes-related oxidative stress and rod, but not choroidal, pathophysiology.