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Evidence of BrdU Positive Retinal Neurons after Application of an Alpha7 Nicotinic Acetylcholine Receptor Agonist

机译:应用Alpha7烟碱型乙酰胆碱受体激动剂后BrdU阳性视网膜神经元的证据

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摘要

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.
机译:由于疾病或年龄造成的不可逆视力下降导致生活质量下降。本研究中的实验检验了以下假设:α7烟碱型乙酰胆碱受体激动剂PNU-282987在没有视网膜损伤或外源性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。使用针对BrdU,视网膜神经节细胞,祖细胞和Müller胶质细胞的抗体,该研究结果表明,成年Long Evans大鼠滴眼液应用PNU-282987后会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,即经过PNU-282987处理后源自Müller胶质细胞的祖细胞可以分化并迁移至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alpha7 nAChR拮抗剂甲基甲基卡康尼汀治疗视网膜,则BrdU阳性细胞会明显减少。由于成年哺乳动物的神经元通常不会再生或增殖,因此这些结果对逆转由于神经退行性疾病或衰老过程导致的视力丧失产生了影响,从而改善了数百万患者的生活质量。

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