Evidence of BrdU-positive retinal neurons after application of an Alpha7 nicotinic acetylcholine receptor agonist.
Evidence of BrdU-positive retinal neurons after application of an Alpha7 nicotinic acetylcholine receptor agonist.
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DOI：
10.1016/j.neuroscience.2017.01.029
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发表时间：
2017-03-27
期刊：
影响因子：
3.3
通讯作者：
Linn CL
中科院分区：
文献类型：
--
作者：
Webster MK;Cooley-Themm CA;Barnett JD;Bach HB;Vainner JM;Webster SE;Linn CL
由于疾病或年龄导致的不可逆转的视力丧失会导致生活质量下降。本研究中的实验验证了以下假设：α7 烟碱乙酰胆碱受体激动剂 PNU-282987 在没有视网膜损伤或外源生长因子的情况下导致成年哺乳动物视网膜中视网膜神经元的生成。利用抗 BrdU、视网膜神经节细胞、祖细胞和米勒胶质细胞的抗体，本研究结果表明，在成年 Long Evans 大鼠中滴眼 PNU-282987 后，会以剂量依赖性方式产生多种类型的视网膜细胞和神经元。这项研究的结果提供了证据，证明源自 Müller 胶质细胞的祖细胞在经过 PNU-282987 处理后会分化并迁移到感光细胞和视网膜神经节细胞层。如果在激动剂治疗之前用 α7 nAChR 拮抗剂甲基lycaconitine 治疗视网膜，BrdU 阳性细胞会显着减少。由于成年哺乳动物神经元通常不会再生或增殖，因此这些结果对于逆转因神经退行性疾病或衰老过程导致的视力丧失，从而改善数百万患者的生活质量具有重要意义。
Irreversible vision loss due to disease or age is responsible for a reduced quality of life. The experiments in this study test the hypothesis that the α7 nicotinic acetylcholine receptor agonist, PNU-282987, leads to the generation of retinal neurons in an adult mammalian retina in the absence of retinal injury or exogenous growth factors. Using antibodies against BrdU, retinal ganglion cells, progenitor cells and Müller glia, the results of this study demonstrate that multiple types of retinal cells and neurons are generated after eye drop application of PNU-282987 in adult Long Evans rats in a dose-dependent manner. The results of this study provide evidence that progenitor cells, derived from Müller glia after treatment with PNU-282987, differentiate and migrate to the photoreceptor and retinal ganglion cell layers. If retinas were treated with the alpha7 nAChR antagonist, methyllycaconitine, before agonist treatment, BrdU positive cells were significantly reduced. As adult mammalian neurons do not typically regenerate or proliferate, these results have implications for reversing vision loss due to neurodegenerative disease or the aging process to improve the quality of life for millions of patients.