Antioxidant or neurotrophic factor treatment preserves function in a mouse model of neovascularization-associated oxidative stress
Antioxidant or neurotrophic factor treatment preserves function in a mouse model of neovascularization-associated oxidative stress
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DOI：
10.1172/jci35977
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发表时间：
2009-03-01
影响因子：
15.9
通讯作者：
Friedlander, Martin
中科院分区：
文献类型：
--
作者：
Dorrell, Michael I.;Aguilar, Edith;Friedlander, Martin
在几种疾病状态下，血管的异常生长与局部神经元变性有关。这在诸如视网膜血管瘤增生（RAP）和黄斑毛细血管扩张（MacTel）的眼部疾病中尤其如此，其中尽管没有大规模渗漏或出血，但异常新生血管形成（NV）与局部神经元功能障碍相关。我们在这里描述了一种视网膜表型与功能障碍的VLDL受体（Vidir（-/-）小鼠），非常类似于人类视网膜疾病，其中异常的视网膜内和视网膜下NV与感光细胞死亡。这种细胞死亡证明了减少锥，并在较小程度上，视杆视蛋白表达和异常视网膜电图。视网膜内血管异常区域的细胞死亡与氧化应激相关标志物的增加有关。口服抗氧化剂补充保护感光细胞变性和保存视网膜功能，尽管异常的视网膜内和视网膜下血管的持续存在。我们认为是新颖的，Muller细胞为基础的，重要的神经营养化合物特异性地传递到NV位点也具有神经保护作用。这些观察结果表明，继发于NV的神经元损失可以通过使用简单的抗氧化剂饮食措施或基于细胞的神经营养因子递送来预防，即使潜在的血管表型没有改变。
In several disease states, abnormal growth of blood vessels is associated with local neuronal degeneration. This is particularly true in ocular diseases such as retinal angiomatous proliferation (RAP) and macular telangiectasia (MacTel), in which, despite the absence of large-scale leakage or hemorrhage, abnormal neovascularization (NV) is associated with local neuronal dysfunction. We describe here a retinal phenotype in mice with dysfunctional receptors for VLDL (Vidir(-/-) mice) that closely resembles human retinal diseases in which abnormal intra- and subretinal NV is associated with photoreceptor cell death. Such cell death was evidenced by decreased cone and, to a lesser extent, rod opsin expression and abnormal electroretinograms. Cell death in the region of intraretinal vascular abnormalities was associated with an increased presence of markers associated with oxidative stress. Oral antioxidant supplementation protected against photoreceptor degeneration and preserved retinal function, despite the continued presence of abnormal intra- and subretinal vessels. What we believe to be novel, Muller cell-based, vitally mediated delivery of neurotrophic compounds specifically to sites of NV was also neuroprotective. These observations demonstrate that neuronal loss secondary to NV can be prevented by the use of simple antioxidant dietary measures or cell-based delivery of neurotrophic factors, even when the underlying vascular phenotype is not altered.