作者: Robert N Frank
DOI: 10.1016/S0002-9394(02)01321-1
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摘要: Abstract PURPOSE: To review the evidence supporting a role for beta (β) isoform of protein kinase C (PKC) in pathogenesis diabetic retinopathy and possible therapeutic benefit inhibiting this enzyme. DESIGN: Brief literature research suggesting potential use systemic inhibitors β PKC as medical therapy to prevent progression retinopathy. consideration is given previous, primarily clinical, studies dealing with other therapies disease. RESULTS: Kinases transfer terminal, “high energy,” phosphate group ATP site on target protein, thereby activating which may be an enzyme, cell membrane receptor, or ion transport channel. The family such enzymes that require specific activator molecules, including diacylglycerol, whose intracellular concentration substantially increased during hyperglycemia diabetes. Protein Cβ present at high levels retina. Increased activation perhaps by producing tissue hypoxia, leads expression vascular endothelial growth factor, mitogen increases proliferation cells leading neovascularization enhances breakdown blood-retinal barrier, resulting macular edema. CONCLUSIONS: By interfering above biochemical pathways, retard development Because members are found throughout body, generalized inhibitor likely toxic. However, PKCβ act effectively within retina have favorable toxicity profile. Two phase III randomized controlled clinical trials now progress, attempting evaluate efficacy approach preventing progression, inducing regression, “nonclinically significant” edema severe nonproliferative