Molecular biological analysis and treatment for diabetic retinopathy

糖尿病视网膜病变是成年人失明的主要原因。我们研究了2型糖尿病模型SDT（自发性糖尿病Torii）大鼠的视网膜变化及其控制糖尿病视网膜病变的分子机制。在一些SDT大鼠的眼睛中发现了与人类增殖性糖尿病视网膜病变（PDR）相似的增殖组织。然而，SDT大鼠视网膜新生血管发生率低，视网膜非灌注区发育不良。SDT大鼠视网膜中血管内皮生长因子（VEGF）和血管生成抑制剂色素上皮衍生因子（PEDF）的表达均升高。PEDF抑制vegf诱导的白细胞停滞。因此，SDT大鼠视网膜中高水平的PEDF可能导致新生血管形成的发生率低，并且没有非灌注区域，这与人类典型的糖尿病视网膜病变不同。在人PDR组织中，VEGF和PEDF均有强表达，但分布不同。血小板衍生微粒（PDMPs）刺激凝血级联并增加白细胞和内皮细胞的粘附，单核细胞衍生微粒（MDMPs）从活化的单核细胞释放并增强促凝活性。这些活动是糖尿病视网膜病变发展的关键事件。PDMPs和MDMPs相互关联，也与活化血小板（CD62P和CD63）和粘附分子（p -选择素和ICAM-1）相关。PDMPs和MDMPs随着糖尿病视网膜病变的进展而升高。因此，MDMPs和PDMPs水平的升高可能会加速糖尿病视网膜病变的进展。

Diabetic retinopathy is a major cause of blindness in adults. We investigate the retinal changes in SDT (Spontaneously Diabetic Torii) rats, a model of type 2 diabetic mellitus, and the molecular mechanisms controlling the diabetic retinopathy. Propliferative tissues that are similar to human proliferative diabetic retinopathy (PDR) are found in eyes of some of the SDT rats. However, SDT rats have a low incidence of retinal neovascularization and poor development of retinal non-perfused areas. Expression of vascular endothelial growth factor (VEGF), a major angiogenic stimulator, and pigment epithelium-derived factor (PEDF), an angiogenic inhibitor, were both increased in the retina of SDT rats. PEDF inhibited the VEGF-induced leukostasis. Thus, the high levels of PEDF in the retina of SDT rats may contribute to the low incidence of neovascular formation and absence of non-perfused areas that did not match the typical diabetic retinopathy in humans. In human PDR tissues, VEGF and PEDF were both strongly expressed, but the distribution was different.Platelet-derived microparticles (PDMPs) stimulate the coagulation cascade and increase leukocyte and endothelial cell adhesions, and monocytes-derived microparticles (MDMPs) are released from activated monocytes and enhance the procoagulant activity. These activities are key events in the development of diabetic retinopathy. PDMPs and MDMPs are correlated with each other and also correlated with activated platelet (CD62P and CD63) and adhesion molecules (P-selectin and ICAM-1). PDMPs and MDMPs are increased according to the progression of diabetic retinopathy. Therefore, increased levels of MDMPs and PDMPs may accelerate the progression of diabetic retinopathy.