Increased basement membrane thickness, pericyte ghosts, and loss of retinal thickness and cells in dopamine beta hydroxylase knockout mice
Increased basement membrane thickness, pericyte ghosts, and loss of retinal thickness and cells in dopamine beta hydroxylase knockout mice
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DOI：
10.1016/j.exer.2008.12.015
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发表时间：
2009-06-01
影响因子：
3.4
通讯作者：
Smith, Christopher P.
中科院分区：
文献类型：
--
作者：
Steinle, Jena J.;Kern, Timothy S.;Smith, Christopher P.
糖尿病可导致交感神经损伤，我们先前已经证明，实验性交感神经切除术可在视网膜中产生类似于早期糖尿病中所见的毛细血管异常。我们假设糖尿病引起的交感神经系统的损失，至少部分交感神经递质去甲肾上腺素（NE），有助于糖尿病视网膜血管和神经异常的发展。因此，我们预测缺乏NE的非糖尿病动物将发生与糖尿病视网膜病变特征相似的微血管和神经变化。为了测试这一点，在5个月大时评估来自非糖尿病多巴胺β羟化酶（Dbh，Dbh（-/-））敲除小鼠及其同窝对照的视网膜的糖尿病样毛细血管和神经变化。Dbh的基因缺失导致视网膜厚度和视网膜神经节细胞层（视网膜中央区域）中的细胞数量显著减少。Dbh（-/-）小鼠视网膜毛细血管基底膜及周细胞影数明显增多。这些结果提供了证据，交感神经传递的损失可能有助于糖尿病视网膜病变的微血管和神经的变化。交感神经传递的恢复可能是一个新的目标，治疗干预，以抑制早期阶段的糖尿病视网膜病变。(C)2009爱思唯尔有限公司保留所有权利。
Diabetes can cause damage to sympathetic nerves, and we have previously shown that experimental sympathectomy can produce capillary abnormalities in the retina similar to those seen in early diabetes. We postulate that the diabetes-induced loss of the sympathetic system, and at least in part the sympathetic neurotransmitter norepinephrine (NE), contributes to the development of retinal vascular and neural abnormalities in diabetes. Thus, we predict that non-diabetic animals that lack NE will develop microvascular and neural changes that are similar to those that are characteristic of diabetic retinopathy. To test this, retinas from non-diabetic dopamine beta hydroxylase (Dbh, Dbh(-/-)) knockout mice and their littermate controls were assessed for diabetic-like capillary and neural changes at 5 months of age. Genetic deletion of Dbh resulted in a significant decrease in retinal thickness and number of cells in the retinal ganglion cell layer (central retinal region). In addition, the number of pericyte ghosts and the basement membrane of retinal capillaries were significantly increased in the Dbh(-/-) mice. These results provide evidence that loss of sympathetic neurotransmission may contribute to the microvascular and neural changes of diabetic retinopathy. Restoration of sympathetic neurotransmission may be a new target for therapeutic intervention to inhibit the early phases of diabetic retinopathy. (C) 2009 Elsevier Ltd. All rights reserved.