Plasma kallikrein mediates retinal vascular dysfunction and induces retinal thickening in diabetic rats

Abstract

OBJECTIVE—Plasma kallikrein (PK) has been identified in vit-reous fluid obtained from individuals with diabetic retinopathy and has been implicated in contributing to retinal vascular dys-function. In this report, we examined the effects of PK on retinal vascular functions and thickness in diabetic rats. RESEARCH DESIGN AND METHODS—We investigated the effects of a selective PK inhibitor, ASP-440, and C1 inhibitor (C1-INH), the primary physiological inhibitor of PK, on retinal vascular permeability (RVP) and hemodynamics in rats with streptozotocin-induced diabetes. The effect of intravitreal PK in-jection on retinal thickness was examined by spectral domain op-tical coherence tomography. RESULTS—Systemic continuous administration of ASP-440 for 4 weeks initiated at the time of diabetes onset inhibited RVP by 42 % (P = 0.013) and 83 % (P, 0.001) at doses of 0.25 and 0.6 mg/k