Roufail E, Soulis T, Boel E, Cooper M E, Rees S
Department of Anatomy and Cell Biology, University of Melbourne, Parkville, Victoria, Australia.
Diabetologia. 1998 Dec;41(12):1419-25. doi: 10.1007/s001250051087.
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.
据报道，神经元型一氧化氮合酶免疫反应性（nNOS-IR）神经元与视网膜血管系统密切相关，有人提出这些神经元的激活可能是视网膜血流与代谢相联系的机制。此外，先前已表明糖尿病视网膜中晚期糖基化终产物（AGEs）增加，而氨基胍（AG）作为晚期糖基化抑制剂，已被证明可减弱AGE积累的发展以及实验性糖尿病视网膜病变的进展。本研究使用NADPH黄递酶（NADPHd）组织化学方法，研究了短期（1周和3周）和长期（32周）糖尿病对视网膜中含nNOS神经元的影响。此外，在短期和长期对照及糖尿病大鼠中，研究了氨基胍（一种晚期糖基化和NOS抑制剂）和NG-硝基-L-精氨酸甲酯（L-NAME）（一种非选择性NOS抑制剂）对视网膜中含nNOS神经元的作用。在另一项研究中，在短期（3周）糖尿病大鼠中研究了2,3-二氨基吩嗪（NN0028）（一种晚期糖基化抑制剂，但不是NOS抑制剂）的作用。糖尿病一周后，每个视网膜中NADPHd阳性神经元的数量减少，长期糖尿病大鼠中仍保持减少，强化胰岛素治疗使血糖正常的糖尿病大鼠未观察到这种效应。用氨基胍或NN0028治疗糖尿病动物可防止含nNOS神经元数量的减少，L-NAME未重现这种效应。这些研究表明，AG恢复含nNOS视网膜神经元数量的作用是通过抑制AGE形成介导的。含nNOS神经元的减少可能导致糖尿病中发生的血流自动调节改变。
