Plasma Kallikrein Inhibitor May Help Treat Diabetic Retinopathy

diabetic retinopathyDiabetic retinopathy – damage to blood vessels in the retina – is the most common diabetic eye disease and is a leading cause of vision loss and blindness in those of working age. Increased retinal vascular permeability is characteristic of diabetic retinopathy and can lead to diabetic macular oedema. Hypertension is a major risk factor for diabetic retinopathy and contributes to a variety of other retinal diseases in the absence of diabetes mellitus. Involvement of both the renin-angiotensin system and the kallikrein-kinin system in diabetic retinopathy has been suggested, and there is evidence indicating that angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blockers reduce the risk of disease progression, both in the presence and absence of hypertension. Using a specific inhibitor, ASP-440, scientists from the Joslin Diabetes Center and ActiveSite Pharmaceuticals have now demonstrated that inhibition of the protease, plasma kallikrein, may provide a new therapeutic approach for the treatment of diabetic retinopathy.

ASP-440Plasma kallikrein levels were found to be increased in the retina of rats with hypertension induced by angiotensin II, and the animals also showed increased retinal vascular permeability. Treatment with the angiotensin II receptor antagonist, candesartan, reduced retinal vascular permeability stimulated by angiotensin II by almost 80%. Continuous systemic administration of ASP-440 via a subcutaneous pump decreased hypertension-induced retinal vascular permeability by a similar amount, suggesting that systemic inhibition of plasma kallikrein may provide a new approach for treating blood-retinal barrier dysfunction caused by high blood pressure.

The study is published in full in the February 1st edition of the journal Hypertension.