title: The kallikrein-kinin system in diabetic retinopathy.
abstract: Diabetic retinopathy (DR) is a major microvascular complication associated with type 1 and type 2 diabetes mellitus, which can lead to visual impairment and blindness. Current treatment strategies for DR are mostly limited to laser therapies, steroids, and anti-VEGF agents, which are often associated with unwanted side effects leading to further complications. Recent evidence suggests that kinins play a primary role in the development of DR through enhanced vascular permeability, leukocytes infiltration, and other inflammatory mechanisms. These deleterious effects are mediated by kinin B1 and B2 receptors, which are expressed in diabetic human and rodent retina. Importantly, kinin B1 receptor is virtually absent in sane tissue, yet it is induced and upregulated in diabetic retina. These peptides belong to the kallikrein-kinin system (KKS), which contains two separate and independent pathways of regulated serine proteases, namely plasma kallikrein (PK) and tissue kallikrein (TK) that are involved in the biosynthesis of bradykinin (BK) and kallidin (Lys-BK), respectively. Hence, ocular inhibition of kallikreins or antagonism of kinin receptors offers new therapeutic avenues in the treatment and management of DR. Herein, we present an overview of the principal features and known inflammatory mechanisms associated with DR along with the current therapeutic approaches and put special emphasis on the KKS as a new and promising therapeutic target due to its link with key pathways directly associated with the development of DR.
authors.forename: Menakshi
authors.initials: M
authors.lastname: Bhat
authors.forename: Mylène
authors.initials: M
authors.lastname: Pouliot
authors.forename: Réjean
authors.initials: R
authors.lastname: Couture
authors.forename: Elvire
authors.initials: E
authors.lastname: Vaucher
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D003930:Diabetic Retinopathy / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D006801:Humans; D007610:Kallikreins / Q000378:metabolism*; D007705:Kinins / Q000378:metabolism*; D012160:Retina / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D012171:Retinal Vessels / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D015398:Signal Transduction; D014785:Vision, Ocular
chemical_list: D000893:Anti-Inflammatory Agents; D007705:Kinins; D007610:Kallikreins