ACE inhibition salvages the visual loss caused by diabetes.
OBJECTIVE
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.
Bui
B V
BV
Department of Optometry and Vision Sciences, University of Melbourne, Victoria, 3010, Australia.
Armitage
J A
JA
Tolcos
M
M
Cooper
M E
ME
Vingrys
A J
AJ
D000465:Algorithms; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000473:pathology; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000503:physiopathology; D004596:Electroretinography; D006146:Guanidines / Q000627:therapeutic use; D020913:Perindopril / Q000627:therapeutic use*; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000503:physiopathology; D014786:Vision Disorders / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology
D000806:Angiotensin-Converting Enzyme Inhibitors; D006146:Guanidines; C004479:pimagedine; D020913:Perindopril