我们的目的是确定血浆脂蛋白,在渗入视网膜并通过糖化和氧化修饰后,有助于1型糖尿病小鼠模型中糖尿病视网膜病变的发展。
为了模拟血浆脂蛋白向视网膜组织的渗透,链脲佐菌素诱导的糖尿病和非糖尿病小鼠模型被玻璃体内注射人高度氧化糖化低密度脂蛋白(HOG-LDL),Native-(N-)LDL,或车辆PBS。视网膜组织学,在随后的14天内评估视网膜电图(ERG)和生化标志物.
玻璃体内施用N-LDL和PBS对糖尿病或非糖尿病动物的视网膜结构或功能没有影响。在非糖尿病小鼠中,HOG-LDL引起短暂的炎症反应而不改变视网膜功能,但是在糖尿病小鼠中它引起了严重的,进行性视网膜损伤,形态异常,ERG更改,血管渗漏,血管内皮生长因子过表达,胶质增生,内质网应激,和凋亡倾向。
糖尿病赋予玻璃体内注射修饰的LDL对视网膜损伤的易感性。这些数据增加了现有的证据,修饰的血浆脂蛋白有助于糖尿病视网膜病变的传播。玻璃体内递送HOG-LDL模拟已知存在的压力,除了高血糖,一旦血-视网膜屏障受损,人类糖尿病视网膜病变。
We aimed to determine whether plasma lipoproteins, after leakage into the retina and modification by glycation and oxidation, contribute to the development of diabetic retinopathy in a mouse model of type 1 diabetes.
To simulate permeation of plasma lipoproteins into retinal tissues, streptozotocin-induced mouse models of diabetes and non-diabetic mice were challenged with intravitreal injection of human \'highly-oxidised glycated\' low-density lipoprotein (HOG-LDL), native- (N-) LDL, or the vehicle PBS. Retinal histology, electroretinography (ERG) and biochemical markers were assessed over the subsequent 14 days.
Intravitreal administration of N-LDL and PBS had no effect on retinal structure or function in either diabetic or non-diabetic animals. In non-diabetic mice, HOG-LDL elicited a transient inflammatory response without altering retinal function, but in diabetic mice it caused severe, progressive retinal injury, with abnormal morphology, ERG changes, vascular leakage, vascular endothelial growth factor overexpression, gliosis, endoplasmic reticulum stress, and propensity to apoptosis.
Diabetes confers susceptibility to retinal injury imposed by intravitreal injection of modified LDL. The data add to the existing evidence that extravasated, modified plasma lipoproteins contribute to the propagation of diabetic retinopathy. Intravitreal delivery of HOG-LDL simulates a stress known to be present, in addition to hyperglycaemia, in human diabetic retinopathy once blood-retinal barriers are compromised.