Molecular biological analysis and treatment for diabetic retinopathy

糖尿病视网膜病变是成人失明的主要原因。我们研究了2型糖尿病模型--自发性糖尿病大鼠视网膜的变化，并探讨了糖尿病视网膜病变的分子控制机制。在一些SDT大鼠的眼睛中发现了类似于人类增殖性糖尿病视网膜病变(PDR)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。血管生成主要刺激因子血管内皮生长因子(VEGF)和血管生成抑制因子色素上皮衍生因子(PEDF)在SDT大鼠视网膜中的表达均增加。PEDF可抑制血管内皮细胞生长因子诱导的白血球沉积。因此，SDT大鼠视网膜中高水平的PEDF可能是导致新生血管形成的低发生率以及缺乏与典型的人类糖尿病视网膜病变不匹配的非灌注区的原因之一。在人PDR组织中，VEGF和PEDF均有较强的表达，但分布不同。血小板衍生微粒(PDMPs)刺激凝血级联反应，增加白细胞与内皮细胞的黏附，单核细胞衍生微粒(MDMPs)从激活的单核细胞中释放出来，增强促凝血活性。这些活动是糖尿病视网膜病变发展过程中的关键事件。PDMPs和MDMPs相互关联，并与活化的血小板(CD62p和CD63)和黏附分子(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增加。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.