Laboratory of Retinal Neurochemistry and Experimental Ophthalmology, Department of Human Biochemistry, School of Medicine/CEFyBO, University of Buenos Aires/CONICET, Buenos Aires, Argentina.
J Pineal Res. 2013 Mar;54(2):179-89. doi: 10.1111/jpi.12008. Epub 2012 Sep 4.
Diabetic retinopathy (DR) is a leading cause of acquired blindness in adults, mostly affected by type 2 diabetes mellitus (T2DM). We have developed an experimental model of early T2DM in adult rats which mimics some features of human T2DM at its initial stages and provokes significant retinal alterations. The aim of this work was to analyze the effect of melatonin on retinal changes induced by the moderate metabolic derangement. For this purpose, adult male Wistar rats received a control diet or 30% sucrose in the drinking water. Three weeks after this treatment, animals were injected with vehicle or streptozotocin (STZ, 25 mg/kg). One day or 3 wk after vehicle or STZ injection, animals were subcutaneously implanted with a pellet of melatonin. Fasting and postprandial glycemia, and glucose, and insulin tolerance tests were analyzed. At 12 wk of treatment, animals which received a sucrose-enriched diet and STZ showed significant differences in metabolic tests, as compared with control groups. Melatonin, which did not affect glucose metabolism in control or diabetic rats, prevented the decrease in the electroretinogram a-wave, b-wave, and oscillatory potential amplitude, and the increase in retinal lipid peroxidation, NOS activity, TNFα, Müller cells glial fibrillary acidic protein, and vascular endothelial growth factor levels. In addition, melatonin prevented the decrease in retinal catalase activity. These results indicate that melatonin protected the retina from the alterations observed in an experimental model of DR associated with type 2 diabetes.
糖尿病视网膜病变（DR）是成年人后天失明的主要原因，主要受 2 型糖尿病（T2DM）影响。我们在成年大鼠中建立了早期 T2DM 的实验模型，该模型模拟了人类 T2DM 早期的某些特征，并引起了明显的视网膜改变。本研究的目的是分析褪黑素对中度代谢紊乱引起的视网膜变化的影响。为此，雄性 Wistar 大鼠给予对照饮食或在饮用水中添加 30%的蔗糖。经过 3 周的这种处理后，动物被注射载体或链脲佐菌素（STZ，25mg/kg）。在注射载体或 STZ 后 1 天或 3 周，动物皮下植入褪黑素丸。分析空腹和餐后血糖、葡萄糖和胰岛素耐量试验。在 12 周的治疗后，接受富含蔗糖饮食和 STZ 的动物在代谢测试中与对照组相比显示出明显的差异。褪黑素不会影响对照或糖尿病大鼠的葡萄糖代谢，但可预防视网膜电图 a 波、b 波和振荡电位幅度的降低，以及视网膜脂质过氧化、NOS 活性、TNFα、Müller 细胞胶质纤维酸性蛋白和血管内皮生长因子水平的升高。此外，褪黑素可预防视网膜过氧化氢酶活性的降低。这些结果表明，褪黑素可保护视网膜免受与 2 型糖尿病相关的 DR 观察到的改变。
