Laspas Panagiotis, Sniatecki Jan J, Brochhausen Christoph, Steege Andreas, Goloborodko Evgeny, Kordasz Marcin L, Grus Franz H, Pfeiffer Norbert, Gericke Adrian
Department of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany,
J Mol Neurosci. 2015 Jun;56(2):472-9. doi: 10.1007/s12031-015-0524-7. Epub 2015 Feb 28.
Pharmacological activation of the M1 muscarinic receptor subtype was suggested to promote the survival of retinal neurons. We examined the hypothesis that the M1 receptor is crucial for retinal neuron survival in vivo by using mice devoid of the M1 receptor gene. Muscarinic receptor gene expression was determined in the retina using real-time PCR. The amount of neurons in the retinal ganglion cell layer and of axons in the optic nerve was determined in retinal wholemounts stained with cresyl blue and in optic nerve cross-sections stained with toluidine blue, respectively. mRNA of all five muscarinic receptor subtypes (M1-M5) was detected in the retina from wild-type mice. Remarkably, M2 and M3 receptor mRNA were most abundant. In retinas from M1 receptor-deficient mice, M4 receptor mRNA expression was increased compared to that of wild-type mice, while no marked changes in the mRNA expression levels of the other muscarinic receptor subtypes were observed. The amount of cells in the retinal ganglion cell layer and the amount of axons in the optic nerve did not differ between M1 receptor-deficient and wild-type mice. The present findings suggest that the M1 receptor is not essential for the survival of retinal neurons in vivo.
M1毒蕈碱受体亚型的药理学激活被认为可促进视网膜神经元的存活。我们通过使用缺乏M1受体基因的小鼠，检验了M1受体对体内视网膜神经元存活至关重要这一假说。使用实时PCR测定视网膜中的毒蕈碱受体基因表达。分别在经甲酚紫染色的视网膜整装片和经甲苯胺蓝染色的视神经横切面上，测定视网膜神经节细胞层中的神经元数量和视神经中的轴突数量。在野生型小鼠的视网膜中检测到了所有五种毒蕈碱受体亚型（M1 - M5）的mRNA。值得注意的是，M2和M3受体mRNA最为丰富。在M1受体缺陷小鼠的视网膜中，与野生型小鼠相比，M4受体mRNA表达增加，而未观察到其他毒蕈碱受体亚型的mRNA表达水平有明显变化。M1受体缺陷小鼠和野生型小鼠之间，视网膜神经节细胞层中的细胞数量和视神经中的轴突数量没有差异。目前的研究结果表明，M1受体对体内视网膜神经元的存活并非必不可少。
