Role of the angiotensin II type 1 receptor in the pathogenesis of diabetic retinopathy: effects of blood pressure control and beyond.
Diabetic retinopathy is characterized by both functional and morphological changes in the retinal microvessels that can lead to macular edema, neovascularization, and vision loss. Hypertension has been identified as a major risk factor for diabetic retinopathy and randomized clinical trials have shown that reduction of blood pressure using angiotensin converting enzyme (ACE) inhibitors reduces the progression of diabetic retinopathy. The major components of the renin-angiotensin system have been identified in ocular tissues. Activation of angiotensin II type 1 (AT1) receptors expressed on retinal endothelial cells and pericytes has been implicated in contributing to the microvascular abnormalities in diabetic retinopathy. We have examined the experimental and clinical evidence for the role of the renin-angiotensin system in the pathogenesis of diabetic retinopathy, including the effects of ACE inhibition and AT1-receptor antagonism on diabetes-induced abnormalities in retinal hemodynamics, vascular permeability, and leukostasis; retinal neovascularization in rodent models of oxygen-induced retinopathy; and results from randomized clinical trials that have investigated the effects of ACE inhibitors on the progression of diabetic retinopathy in diabetic patients in the absence or presence of hypertension. The effects of AT1-receptor antagonism on the retina have been attributed to decreases in systemic blood pressure and the concomitant reduction in mechanical vascular stretch, in addition to the intraocular effects blocking AT1-receptor stimulation of retinal endothelial cells and pericytes. Results from the current DIabetic REtinopathy Candesartan Trials program will evaluate the potential of the AT1-receptor as a therapeutic target for diabetic retinopathy.
Clermont
Allen
A
Research Division, Boston, Massachusetts 02215, USA.
Bursell
Sven-Erik
SE
Feener
Edward P
EP
D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D002199:Capillary Permeability; D003930:Diabetic Retinopathy / Q000209:etiology*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000502:physiology; D012160:Retina / Q000378:metabolism
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D044140:Receptor, Angiotensin, Type 1; D005947:Glucose