Webster Mark K, Cooley-Themm Cynthia A, Barnett Joseph D, Bach Harrison B, Vainner Jessica M, Webster Sarah E, Linn Cindy L
Western Michigan University, Department of Biological Sciences, Kalamazoo, MI 49008, USA.
Western Michigan University, Department of Biological Sciences, Kalamazoo, MI 49008, USA.
Neuroscience. 2017 Mar 27;346:437-446. doi: 10.1016/j.neuroscience.2017.01.029. Epub 2017 Jan 29.
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.
疾病或衰老导致的不可逆视力丧失会降低生活质量。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在无视网膜损伤或外源性生长因子的情况下,能促使成年哺乳动物视网膜中产生视网膜神经元。使用抗BrdU、视网膜神经节细胞、祖细胞和穆勒胶质细胞的抗体,本研究结果表明,在成年Long Evans大鼠中,以剂量依赖的方式对其滴眼施用PNU-282987后,会产生多种类型的视网膜细胞和神经元。本研究结果提供了证据,表明经PNU-282987处理后从穆勒胶质细胞衍生而来的祖细胞会分化并迁移到光感受器和视网膜神经节细胞层。如果在激动剂处理前先用α7 nAChR拮抗剂甲基lycaconitine处理视网膜,BrdU阳性细胞会显著减少。由于成年哺乳动物神经元通常不会再生或增殖,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、改善数百万患者的生活质量具有重要意义。