摘要糖尿病视网膜病变(DR)神经损伤的病理改变主要包括神经细胞损伤和胶质细胞增生,均出现在DR早期,可由高血糖刺激直接引起;两者相互促进,导致DR进一步加重.DR神经细胞损伤的分子机制研究主要集中于炎症、氧化应激、内质网应激、晚期糖基化终末产物的形成增加等细胞外环境的改变及相关的信号通路,其主要结局为凋亡和自噬.神经胶质细胞在神经细胞损伤后反应性激活,表现为细胞形态、数量及胞内蛋白表达水平的改变.在非增生型DR中,神经细胞损伤较轻,胶质细胞轻度活化增生;而在增生型DR中,胶质细胞明显活化增生,释放大量炎症因子及血管活性物质,导致视神经损伤的进一步加重.细胞外信号调节激酶1/2、c-Fos、p38丝裂原活化蛋白激酶等多条信号通路均与之相关.对这些分子机制及信号通路的研究将有望在细胞水平上调控DR神经损伤的病理改变.

abstractsThe neuroretinal injuries of diabetic retinopathy (DR) include retinal neuronal damage and reactive gliosis,both of which are induced by hyperglycemia and presented as early features of DR.They promote to develop mutually and accelerate the progression of DR.The molecular mechanisms study of neuronal damage mainly focuses on the alterations of extracellular environment and related signaling pathways,include inflammation,oxidative stress,endoplasmic reticulum stress,the formation of advanced glycation end products,glutamate toxicity and so on.These alterations mainly result in neuronal apoptosis and autophagy.The damaged neurons activate the glial cells with apparent changes in morphology,cell counts and the level of intracellular protein expression.In non-proliferative DR,glial cells are moderately hypertrophic and slightly increased in numbers.In proliferative DR,there is a significant rise in glial cell number with enhanced level of inflammatory factors and vascular active substances which lead a further neuronal damage.Signaling pathways of extracellular signal-regulated kinase 1/2,c-Fos and p38 mitogen-activated protein kinase are associated with their activation.Researches on the molecular mechanisms and signaling pathways of the DR will promote controlling the DR progression at the cellular level.