Angiotensin converting enzyme inhibition reduces retinal overexpression of vascular endothelial growth factor and hyperpermeability in experimental diabetes

Abstract

Despite laser photocoagulation therapy, diabetic retinopathy remains a common cause of visual impairment and blindness [1], principally as a consequence of proliferative retinopathy and macular oedema. Although the pathogenesis of these retinal disorders characterized by retinal neovascularization and exudation is incompletely understood, recent evidence has implicated the vascular endothelial growth factor (VEGF), a permeability-inducing and endothelial cell selective angiogenic glycoprotein as a key factor [2±4].Although plasma renin is suppressed in diabetes, experimental evidence suggests that the tissue reninangiotensin system (RAS) is activated in the setting of chronic hyperglycaemia [5] and that its blockade underlies the beneficial effects of angiotensin converting enzyme (ACE) inhibition in diabetic nephropathy [6] and cardiovascular disease [7]. Previous

Diabetic retinopathy

“…Consequently, also based on in vitro evidence that angiotensin II increases glucose uptake by retinal pericytes [100], induces release of VEGF by retinal endothelial cells [101], and that blockade of the renin-angiotensin system could prevent new vessel growth in a transgenic animal model of retinopathy of prematurity [102], an angiotensin-receptor blocker is undergoing a clinical trial appropriately targeted and powered to test its possible role in the primary and secondary prevention of DR.…”

Angiotensin converting enzyme inhibiting therapy is associated with lower vitreous vascular endothelial growth factor concentrations in patients with proliferative diabetic retinopathy

“…To date, there are no published investigations in humans on ACE inhibition therapy and VEGF concentrations in the eye. In rats, ACE inhibitor treat- ment reduced the retinal overexpression of VEGF mRNA both in streptozotocin-induced diabetes [21] and in a retinopathy of prematurity model [25]. ACE inhibitors attenuate the formation of angiotensin II and the break-down of bradykinin.…”

“…The induction of VEGF by angiotensin II requires hyperglycaemic [16] or oxidative conditions [17], which are states that accompany diabetes. In streptozotocin-induced diabetic rats it has been shown that ACE-inhibition reduces the increased concentrations of VEGF mRNA in the retina [21].…”

Angiotensin AT 1 receptor antagonism normalizes retinal blood flow and acetylcholine-induced vasodiliation in normotensive diabetic rats

“…Treatment of spontaneously hypertensive streptozotocin (STZ)-induced diabetic rats with an ACEI or an AT 1 receptor antagonist reduced VEGF and VEGF-R2 expression [5,6]. In addition, ACE inhibition has been shown to reduce retinal VEGF expression in normotensive STZ-induced diabetic rats [7]. These findings suggest that the angiotensin II/AT 1 pathway contributes to increased retinal VEGF expression in diabetes and hypertension and thereby could contribute to increased vascular permeability and neovascularization.…”