Involvement of brain-derived neurotrophic factor in early retinal neuropathy of streptozotocin-induced diabetes in rats: therapeutic potential of brain-derived neurotrophic factor for dopaminergic amacrine cells.
Involvement of brain-derived neurotrophic factor in early retinal neuropathy of streptozotocin-induced diabetes in rats: therapeutic potential of brain-derived neurotrophic factor for dopaminergic amacrine cells.
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DOI：
10.2337/diabetes.53.9.2412
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发表时间：
2004-09
期刊：
影响因子：
7.7
通讯作者：
Masaaki Seki;Takayuki Tanaka;H. Nawa;T. Usui;T. Fukuchi;K. Ikeda;H. Abe;N. Takei
中科院分区：
文献类型：
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作者：
Masaaki Seki;Takayuki Tanaka;H. Nawa;T. Usui;T. Fukuchi;K. Ikeda;H. Abe;N. Takei
虽然神经营养因子已被评估为糖尿病神经并发症的候选治疗药物，但其在糖尿病视网膜病变中的作用尚未得到充分表征。结果发现，链脲佐菌素诱导的糖尿病大鼠视网膜中脑源性神经营养因子（BDNF）的蛋白和mRNA水平分别为正常对照组的49%（P < 0.005）和74%（P < 0.05）。此外，多巴胺能无长突细胞似乎是在糖尿病大鼠视网膜变性，所揭示的酪氨酸羟化酶（TH）的免疫反应。视网膜中总的TH蛋白水平下降到对照组的一半（P < 0.01），反映了多巴胺能无长突细胞密度和TH免疫反应强度的降低。为了证实BDNF减少的神经病理学意义，我们将BDNF蛋白注入糖尿病大鼠的玻璃体腔。眼内注射BDNF可使多巴胺能无长突细胞免于神经变性，并可抵消TH表达的下调，显示其治疗潜力。这些发现表明，糖尿病早期视网膜神经病变涉及BDNF的表达减少，并可以通过这种神经营养因子的外源性供应得到改善。
Although neurotrophins have been assessed as candidate therapeutic agents for neural complications of diabetes, their involvement in diabetic retinopathy has not been fully characterized. We found that the protein and mRNA levels of brain-derived neurotrophic factor (BDNF) in streptozotocin-induced diabetic rat retinas were reduced to 49% (P < 0.005) and 74% (P < 0.05), respectively, of those of normal control animals. In addition, dopaminergic amacrine cells appeared to be degenerating in the diabetic rat retinas, as revealed by tyrosine hydroxylase (TH) immunoreactivity. Overall TH protein levels in the retina were decreased to one-half that of controls (P < 0.01), reflecting reductions in the density of dopaminergic amacrine cells and the intensity of TH immunoreactivity within them. To confirm the neuropathological implications of BDNF reduction, we administered BDNF protein into the vitreous cavities of diabetic rats. Intraocular administration of BDNF rescued dopaminergic amacrine cells from neurodegeneration and counteracted the downregulation of TH expression, demonstrating its therapeutic potential. These findings suggest that the early retinal neuropathy of diabetes involves the reduced expression of BDNF and can be ameliorated by an exogenous supply of this neurotrophin.