Lang Gabriele E, Kampmeier Jürgen
Universitätsklinikum Ulm, Augenklinik.
Klin Monbl Augenheilkd. 2002 Nov;219(11):769-76. doi: 10.1055/s-2002-36328.
Hyperglycemic control in diabetes mellitus is a major key to prevent the development and progression of diabetic retinopathy. One important pathomechanism in the development of diabetic complications is the activation of protein kinase C (PKC) induced by high glucose due to an increased diacylglycerol (DAG) level. Resulting vascular dysfunctions are increased vascular permeability and contractility, increased production of extracellular matrix and cell proliferation. The PKC isoenzyme family plays a fundamental role in the cellular signal transduction via phosphorylation and modification of enzymes, receptors, transcription factors and kinases. The PKC activation influences the gene transcription and ion transport. Different PKC isoenzymes function as mediators but also as inhibitors of the insulin effects. The hyperglycemia induced DAG production seems to predominantly activate PKC-beta in retinal vascular endothelial cells. The development of selective PKC-beta inhibitors enables new pharmacological therapeutical approaches for treatment of diabetic retinopathy. Ongoing clinical studies investigate if the treatment with specific PKC-beta inhibitors can prevent the progression of diabetic retinopathy and diabetic macular edema.
糖尿病中的血糖控制是预防糖尿病视网膜病变发生和发展的关键。糖尿病并发症发生的一个重要病理机制是高血糖通过增加二酰甘油（DAG）水平诱导蛋白激酶C（PKC）激活。由此导致的血管功能障碍包括血管通透性和收缩性增加、细胞外基质产生增加以及细胞增殖。PKC同工酶家族通过对酶、受体、转录因子和激酶的磷酸化和修饰在细胞信号转导中起基本作用。PKC激活影响基因转录和离子转运。不同的PKC同工酶既作为胰岛素作用的介质，也作为其抑制剂。高血糖诱导的DAG产生似乎主要激活视网膜血管内皮细胞中的PKC-β。选择性PKC-β抑制剂的研发为糖尿病视网膜病变的治疗带来了新的药理学治疗方法。正在进行的临床研究调查了用特定的PKC-β抑制剂治疗是否能预防糖尿病视网膜病变和糖尿病黄斑水肿的进展。
