Plasma kallikrein-kinin system and diabetic retinopathy
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Jia Liu
Abstract
Diabetic retinopathy (DR) occurs, to some extent, in most people with at least 20 years’ duration of diabetes mellitus. The progression of DR to its sight-threatening stages is usually associated with the worsening of underlying retinal vascular dysfunction and disease. The plasma kallikrein-kinin system (KKS) is activated during vascular injury, where it mediates important functions in innate inflammation, blood flow, and coagulation. Recent findings from human vitreous proteomics and experimental studies on diabetic animal models have implicated the KKS in contributing to DR. Vitreous fluid from people with advanced stages of DR contains increased levels of plasma KKS components, including plasma kallikrein (PK), coagulation factor XII, and high-molecular-weight kininogen. Both bradykinin B1 and B2 receptor isoforms (B1R and B2R, respectively) are expressed in human retina, and retinal B1R levels are increased in diabetic rodents. The activation of the intraocular KKS induces retinal vascular permeability, vasodilation, and retinal thickening, and these responses are exacerbated in diabetic rats. Preclinical studies have shown that the administration of PK inhibitors and B1R antagonists to diabetic rats ameliorates retinal vascular hyperpermeability and inflammation. These findings suggest that components of plasma KKS are potential therapeutic targets for diabetic macular edema.
©2013 by Walter de Gruyter Berlin Boston
Articles in the same Issue
- Masthead
- Masthead
- Guest Editorial
- Highlight: Kinin 2012 in Paris
- Highlight: Kinin 2012 in Paris
- Plasma kallikrein-kinin system and diabetic retinopathy
- Tissue kallikrein, blood pressure regulation, and hypertension: insight from genetic kallikrein deficiency
- Carboxypeptidase M augments kinin B1 receptor signaling by conformational crosstalk and enhances endothelial nitric oxide output
- Interactions between BdkrB2 and p53 genes in the developing kidney
- Further pharmacological evaluation of a novel synthetic peptide bradykinin B2 receptor agonist
- Role of kinin B2 receptors in opioid-induced hyperalgesia in inflammatory pain in mice
- Clinical impact of an angiotensin I-converting enzyme insertion/deletion and kinin B2 receptor +9/-9 polymorphisms in the prognosis of renal transplantation
- Bifunctional epitope-agonist ligands of the bradykinin B2 receptor
- Pro-angiogenic effect of human kallikrein-related peptidase 12 (KLK12) in lung endothelial cells does not depend on kinin-mediated activation of B2 receptor
- Review
- Mitochondrial pathways in sarcopenia of aging and disuse muscle atrophy
- Research Articles/Short Communications
- Genes and Nucleic Acids
- A genetic variant in the promoter region of miR-34b/c is associated with a reduced risk of colorectal cancer
- Protein Structure and Function
- SH3-mediated targeting of Wrch1/RhoU by multiple adaptor proteins
Articles in the same Issue
- Masthead
- Masthead
- Guest Editorial
- Highlight: Kinin 2012 in Paris
- Highlight: Kinin 2012 in Paris
- Plasma kallikrein-kinin system and diabetic retinopathy
- Tissue kallikrein, blood pressure regulation, and hypertension: insight from genetic kallikrein deficiency
- Carboxypeptidase M augments kinin B1 receptor signaling by conformational crosstalk and enhances endothelial nitric oxide output
- Interactions between BdkrB2 and p53 genes in the developing kidney
- Further pharmacological evaluation of a novel synthetic peptide bradykinin B2 receptor agonist
- Role of kinin B2 receptors in opioid-induced hyperalgesia in inflammatory pain in mice
- Clinical impact of an angiotensin I-converting enzyme insertion/deletion and kinin B2 receptor +9/-9 polymorphisms in the prognosis of renal transplantation
- Bifunctional epitope-agonist ligands of the bradykinin B2 receptor
- Pro-angiogenic effect of human kallikrein-related peptidase 12 (KLK12) in lung endothelial cells does not depend on kinin-mediated activation of B2 receptor
- Review
- Mitochondrial pathways in sarcopenia of aging and disuse muscle atrophy
- Research Articles/Short Communications
- Genes and Nucleic Acids
- A genetic variant in the promoter region of miR-34b/c is associated with a reduced risk of colorectal cancer
- Protein Structure and Function
- SH3-mediated targeting of Wrch1/RhoU by multiple adaptor proteins
