Depletion of nitric oxide synthase-containing neurons in the diabetic retina: reversal by aminoguanidine |
| |
| Authors: | E Roufail T Soulis E Boel M E Cooper S Rees |
| |
| Institution: | (1) Department of Anatomy and Cell Biology, University of Melbourne, Parkville, Victoria, Australia, AU;(2) Department of Ophthalmology, University of Melbourne, Parkville, Victoria, Australia, AU;(3) Department of Medicine, University of Melbourne, Austin and Repatriation Medical Centre (Repatriation Campus) Banksia Street, West Heidelberg, Victoria, Australia, AU;(4) Health Care Discovery, Novo-Nordisk, Bagsvaerd, Denmark, DK |
| |
| Abstract: | Summary A close association of neuronal nitric oxide synthase-immunoreactive (nNOS-IR) neurons with the retinal vasculature has been
reported and it is proposed that activation of these neurons could be the mechanism by which retinal blood flow and metabolism
are linked. Further, advanced glycation end products (AGEs) have previously been shown to be increased in the diabetic retina
and aminoguanidine (AG), an inhibitor of advanced glycation, has been shown to attenuate the development of AGE accumulation
as well as the progression of experimental diabetic retinopathy. This study examined the effects of short (1 and 3 weeks)
and long term (32 weeks) diabetes on nNOS-containing neurons of the retina using NADPH diaphorase (NADPHd) histochemistry.
In addition, the effect of aminoguanidine (an inhibitor of advanced glycation and NOS) and NG-nitro-L-arginine methyl ester (L-NAME) (a non-selective NOS inhibitor) on retinal nNOS-containing neurons was examined in
short and long term control and diabetic rats. In a separate study, the effect of 2,3 diamino-phenazine (NN0028) (an inhibitor
of advanced glycation, but not NOS) was examined in short term (3 weeks) diabetic rats. The number of NADPHd-positive neurons
per retina was reduced after one week of diabetes and remained decreased in long term diabetic rats, an effect not observed
in diabetic rats rendered euglycaemic by intensified insulin treatment. Treatment of diabetic animals with aminoguanidine
or NN0028 prevented the depletion in the nNOS-containing neuron number, an effect not reproduced by L-NAME. These studies
suggest that the action of AG in restoring the number of nNOS-containing retinal neurons is mediated by the inhibition of
AGE formation. The depletion of nNOS-containing neurons may contribute to alterations in the autoregulation of blood flow
which occurs in diabetes. Diabetologia (1998) 41: 1419–1425]
Received: 23 February 1998 and in final revised form: 4 August 1998 |
| |
| Keywords: | Retinopathy advanced glycation blood vessels NADPH diaphorase amacrine cells |
| 本文献已被 SpringerLink 等数据库收录！ |
|
