Aminoguanidine Prevents the Depletion of Neurons Containing Nitric Oxide Synthase in the Streptozotocin Diabetic Rat

Summary Recently, we demonstrated that nitric oxide synthase immunoreactive (NOS-IR) neurons are closely associated with the retinal vasculature and have proposed that these neurons are the mechanism by which retinal blood flow and metabolism are linked. This study examined the effect of diabetes on the population of NADPH diaphorase (NADPHd)-positive (equivalent to NOS-IR) neurons in the retina. Aminoguanidine (AG), an inhibitor of advanced glycation, has been shown to attenuate AGE accumulation as well as the progression of retinal disease in experimental diabetes. It is known that aminoguanidine also inhibits NOS in vitro . This study investigated the effect of diabetes and aminoguanidine (an inhibitor of advanced glycation) or N G -monomethyl-L-arginine (L-NAME) (an inhibitor of NOS), treatment on the population of NAPDHd-positive amacrine cells in the rat retina. Diabetic and control rats were randomized and received no treatment, aminoguanidine or L-NAME for 32 weeks. Diabetic rats had increased serum glucose levels and blood pressure, but lower body weight compared with controls. The number of NADPHd-positive neurons per retina was significantly reduced (−26%) in diabetic rats compared with control rats. Aminoguanidine treatment of diabetic rats restored the number of NADPHd-positive neurons to normal levels at 32 weeks. L-NAME treatment of diabetic animals had no effect on the number of NADPHd-positive neurons. Since the retinoprotective effect of aminoguanidine cannot be reproduced by L-NAME, it is likely to be mediated by a decrease in advanced glycation rather than by inhibition of NOS.