Effect of the M1 Muscarinic Acetylcholine Receptor on Retinal Neuron Number Studied with Gene-Targeted Mice

Pharmacological activation of the M-1 muscarinic receptor subtype was suggested to promote the survival of retinal neurons. We examined the hypothesis that the M-1 receptor is crucial for retinal neuron survival in vivo by using mice devoid of the M-1 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 (M-1-M-5) was detected in the retina from wild-type mice. Remarkably, M-2 and M-3 receptor mRNA were most abundant. In retinas from M-1 receptor-deficient mice, M-4 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 M-1 receptor-deficient and wild-type mice. The present findings suggest that the M-1 receptor is not essential for the survival of retinal neurons in vivo.