The role of protein kinase C in the pathophysiology of diabetic retinopathy

被引:8
作者
Lang, GE [1 ]
Kampmeier, J [1 ]
机构
[1] Univ Ulm Klinikum, Augenklin, D-89075 Ulm, Germany
关键词
protein kinase C (PKC); diacylglycerol (DAG); PKC isoenzymes; LY333531; vitamin E; diabetic retinopathy;
D O I
10.1055/s-2002-36328
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
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.
引用
收藏
页码:769 / 776
页数:8
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