Alternative pathways in the development of diabetic retinopathy: the renin‐angiotensin and kallikrein‐kinin systems

Diabetic retinopathy is a common complication of both type 1 and type 2 diabetes and is the leading cause of blindness in people of working age. Current treatment strategies are mostly limited to laser photocoagulation, which restricts proliferative retinopathic changes but also causes irreversible damage to the retina. This review examines two important pathways involved in regulating vascular function and their role in the development of diabetic retinopathy. One, the renin-angiotensin system, is well known and has established angiogenic effects on the retina that increase in diabetic retinopathy. The other, the kallikrein-kinin system, has recently been found to be important in the development of diabetic retinal complications. This review describes the components of the two signalling networks, examines the current animal model studies investigating the role of these pathways in diabetic retinopathy and reviews the clinical studies that have been undertaken examining systemic inhibition of different points in these pathways. These systems are promising targets for therapies aimed at inhibiting the development of diabetic retinopathy and in the future, combination therapies that take advantage of both pathways might result in new treatment options for this debilitating complication of diabetes.