Berkowitz Bruce A, Roberts Robin, Stemmler Ann, Luan Hongmei, Gradianu Marius
Department of Anatomy and Cell Biology, Wayne State University, Detroit, Michigan 48201, USA.
Invest Ophthalmol Vis Sci. 2007 Oct;48(10):4753-8. doi: 10.1167/iovs.07-0433.
To test the hypothesis that early in the course of diabetes, apparent ion demand within the retina is impaired and may be corrected by alpha-lipoic acid (LPA), a drug that inhibits vascular histopathology.
Intraretinal manganese ion uptake and retinal thickness were measured from high-resolution manganese-enhanced MRI (MEMRI) data of control and streptozocin diabetic male Sprague-Dawley (SD) rats and of control and diabetic female Lewis rats with and without treatment with LPA. In a subgroup of male SD rats, blood-retinal barrier (BRB) integrity was also assessed with dynamic contrast-enhanced MRI. In addition, ion-coupled plasma-mass spectrometry (ICP-MS) was used to measure baseline whole manganese levels from retinas of control and diabetic rats.
Manganese ion uptake by receptor and postreceptor retina was subnormal in each untreated diabetic groups, and these deficiencies could be corrected with LPA treatment. ICP-MS studies found no differences in baseline retinal manganese concentration between control and diabetic rats. In 3-month-old diabetic male SD rats, total and postreceptor retinal thickness increased (P < 0.05) without loss of BRB integrity. In contrast, in untreated and treated diabetic female Lewis rats, retinal thicknesses were normal.
The present results support the hypothesis that LPA can correct the impaired apparent ion demand in experimental diabetic retinopathy.
验证糖尿病病程早期视网膜内表观离子需求受损且可通过α-硫辛酸（LPA）纠正这一假说，α-硫辛酸是一种可抑制血管组织病理学改变的药物。
利用高分辨率锰增强磁共振成像（MEMRI）数据，测量对照及链脲佐菌素诱导糖尿病的雄性Sprague-Dawley（SD）大鼠以及对照及糖尿病雌性Lewis大鼠在接受或未接受LPA治疗情况下的视网膜内锰离子摄取量及视网膜厚度。在雄性SD大鼠亚组中，还通过动态对比增强磁共振成像评估血视网膜屏障（BRB）完整性。此外，采用离子耦合等离子体质谱法（ICP-MS）测量对照及糖尿病大鼠视网膜的基线全锰水平。
各未治疗糖尿病组中，受体及受体后视网膜的锰离子摄取均低于正常水平，而这些缺陷可通过LPA治疗得到纠正。ICP-MS研究发现对照及糖尿病大鼠的基线视网膜锰浓度无差异。在3月龄糖尿病雄性SD大鼠中，受体后视网膜总厚度增加（P < 0.05），且BRB完整性未受损。相比之下，未治疗及治疗后的糖尿病雌性Lewis大鼠视网膜厚度正常。
目前结果支持LPA可纠正实验性糖尿病视网膜病变中受损的表观离子需求这一假说。
