ACE inhibition salvages the visual loss caused by diabetes

Abstract

Aims. We consider the nature of retinal dysfunction in streptozotocin rats and assess the functional benefits of administering an angiotensin enzyme inhibitor or an inhibitor of advanced glycation end product formation. Methods. Sprague-Dawley rats (n=44) were randomly assigned to control (C=12, C p =4, C a =4) and diabetic groups (Streptozotocin, D=24). Diabetes was diagnosed based on a range of physiological and biochemical parameters at 4, 8 and 12 weeks. Streptozotocin animals were administered insulin daily (4 units protophane). Animals were treated with either an Angiotensin Converting Enzyme inhibitor (perindopril, C p =4, D p =8) or an inhibitor of advanced glycation end product formation (aminoguanidine, C a =4, D a =8). Dark-adapted electroretinograms were measured on anaesthetized animals at 12 weeks following streptozotocin treatment. Photoreceptoral and inner retinal responses were extracted, modelled and compared using ANOVA.Results. Streptozotocin injection increased blood glucose, glycosylated haemoglobin, fluid intake and urine volume, whereas body weight was decreased. Perindopril treatment produced improvements (p<0.05) in all indices, whereas aminoguanidine therapy produced some improvement in blood glucose and water intake. Streptozotocin rats showed losses of photoreceptoral-P3 (−27%), postreceptoral-P2 (−15%) and oscillatory potential (−19%) amplitudes of a similar magnitude. Perindopril therapy returned photoreceptoral and inner retinal function to within control limits. However, aminoguanidine treatment gave no significant functional improvement. Conclusions. Our findings provide evidence for a selective neuropathy in diabetes with a primary photoreceptoral lesion. Treatment with perindopril, an angiotensin converting enzyme inhibitor, ameliorates the neuropathy. [Diabetologia (2003) 46:401-408]

Microangiopathy and visual deficits characterize the retinopathy of a spontaneously hypertensive rat model with type 2 diabetes and metabolic syndrome

“…Remarkably, altered function of photoreceptors has also been described in the STZ-induced diabetic rat model based on different findings. [50][51][52] In addition, affected a-and b-wave parameters could be a consequence of impaired blood circulation, which is a characteristic of diabetic retinopathy and may therefore be correlated with the morphologically described microangiopathy. 53 A further striking characteristic of retinopathy in obese animals is its slower progression compared with the insulin-deficient STZ model.…”

Role of NADPH oxidase and ANG II in diabetes-induced retinal leukostasis

“…In particular, the strong reaction observed in the outer layer suggests that one or more of its cellular components responds to ANG II, or to a compound released by the peptide from some other cellular components, with increases in superoxide via NADPH oxidase activation. There are reports suggesting that ANG II is involved in diabetic neuropathies in the retina (8). Perhaps there is a functional relationship between ANG II, superoxide, and retina neuronal function.…”

Role of Nitrosative Stress and Peroxynitrite in the Pathogenesis of Diabetic Complications. Emerging New Therapeutical Strategies

“…Recent studies indicate that the protective effects of angiotensin converting enzyme inhibitors or angiotensin receptor antagonists may go beyond the blood pressure lowering effects of these agents [72][73][74]. Furthermore, ACE inhibition in vivo reduces the apparent formation of peroxynitrite [35].…”