Muller glial dysfunction during diabetic retinopathy in rats is linked to accumulation of advanced glycation end-products and advanced lipoxidation end-products
Muller glial dysfunction during diabetic retinopathy in rats is linked to accumulation of advanced glycation end-products and advanced lipoxidation end-products
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DOI：
10.1007/s00125-010-1971-x
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发表时间：
2011-03-01
期刊：
影响因子：
8.2
通讯作者：
Stitt, A. W.
中科院分区：
文献类型：
--
作者：
Curtis, T. M.;Hamilton, R.;Stitt, A. W.
AGEs和晚期脂氧化终产物（ALE）对糖尿病视网膜中神经元和Muller神经胶质功能障碍的影响尚不清楚。因此，我们试图确定糖尿病期间视网膜Muller神经胶质的功能障碍，并确定AGEs/ALE的抑制是否可以预防它。Sprague-Dawley大鼠分为三组：（1）非糖尿病组;（2）未经治疗的链脲佐菌素诱导的糖尿病组;（3）糖尿病组在糖尿病期间用AGE/ALE抑制剂吡哆胺治疗。糖尿病大鼠视网膜中AGEs和ALE的积累水平高于对照组（p < 0.001）。吡哆胺治疗的糖尿病大鼠的AGE/ALE免疫反应性显着减少。糖尿病还与氧化应激标记物血红素加氧酶-1的上调和Muller神经胶质细胞中神经胶质酸性蛋白的诱导产生有关（p < 0.001）。吡哆胺治疗糖尿病大鼠对这两个变量都有显著的有益作用（p < 0.001）。糖尿病还显著改变了钾内向整流通道Kir4.1和水通道水通道蛋白4到与视网膜毛细血管相互作用的Muller神经胶质末足的正常定位。这些异常被预防吡哆胺treatment.While它是建立在糖尿病视网膜中的AGE/ALE形成与微血管功能障碍，这项研究表明，这些致病加合物也发挥了作用，在穆勒神经胶质功能障碍。
The impact of AGEs and advanced lipoxidation end-products (ALEs) on neuronal and Muller glial dysfunction in the diabetic retina is not well understood. We therefore sought to identify dysfunction of the retinal Muller glia during diabetes and to determine whether inhibition of AGEs/ALEs can prevent it.Sprague-Dawley rats were divided into three groups: (1) non-diabetic; (2) untreated streptozotocin-induced diabetic; and (3) diabetic treated with the AGE/ALE inhibitor pyridoxamine for the duration of diabetes. Rats were killed and their retinas were evaluated for neuroglial pathology.AGEs and ALEs accumulated at higher levels in diabetic retinas than in controls (p < 0.001). AGE/ALE immunoreactivity was significantly diminished by pyridoxamine treatment of diabetic rats. Diabetes was also associated with the up-regulation of the oxidative stress marker haemoxygenase-1 and the induction of glial fibrillary acidic protein production in Muller glia (p < 0.001). Pyridoxamine treatment of diabetic rats had a significant beneficial effect on both variables (p < 0.001). Diabetes also significantly altered the normal localisation of the potassium inwardly rectifying channel Kir4.1 and the water channel aquaporin 4 to the Muller glia end-feet interacting with retinal capillaries. These abnormalities were prevented by pyridoxamine treatment.While it is established that AGE/ALE formation in the retina during diabetes is linked to microvascular dysfunction, this study suggests that these pathogenic adducts also play a role in Muller glial dysfunction.