The kallikrein-kinin system in diabetic retinopathy: lessons for the kidney.
Diabetic retinopathy and diabetic nephropathy are common microvascular complications of diabetes. The kallikrein-kinin system (KKS) has been implicated in the development of both conditions, and, in particular, bradykinin and its receptors have been shown to exert angiogenic and proinflammatory actions. Several of the key processes that underlie the development of diabetic retinopathy, such as increased vascular permeability, edema, neovascularization, and inflammatory changes, have been associated with the KKS, and recent work has shown that components of the KKS, including plasma kallikrein, factor XIIa, and high-molecular-weight kininogen, are present in the vitreous of people with diabetic retinopathy. The role of the KKS in the development of diabetic nephropathy is controversial, with both adverse and protective effects of bradykinin and its receptors reported. The review examines the role of the KKS in pathways central to the development of diabetic retinopathy and compares this with reported actions of this system in diabetic nephropathy. The possibility of therapeutic intervention targeting bradykinin and its receptors as treatment for diabetic microvascular conditions is considered.
Phipps
J A
JA
Department of Medicine, Harvard Medical School and Research Division, Joslin Diabetes Center, Boston, Massachusetts, USA.
Feener
E P
EP
D003928:Diabetic Nephropathies / Q000209:etiology*; D003930:Diabetic Retinopathy / Q000209:etiology*; D006801:Humans; D016234:Kallikrein-Kinin System / Q000502:physiology*