Synergistic Signaling by Light and Acetylcholine in Mouse Iris Sphincter Muscle.
Synergistic Signaling by Light and Acetylcholine in Mouse Iris Sphincter Muscle.
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DOI：
10.1016/j.cub.2017.05.022
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发表时间：
2017-06-19
期刊：
影响因子：
--
通讯作者：
Yau KW
中科院分区：
文献类型：
--
作者：
Wang Q;Yue WWS;Jiang Z;Xue T;Kang SH;Bergles DE;Mikoshiba K;Offermanns S;Yau KW
哺乳动物瞳孔对光反射（PLR）涉及双侧脑回路，由此视神经中的传入光信号最终经由兴奋性胆碱能副交感神经支配驱动虹膜-括约肌-肌肉收缩。此外，PLR在夜间和黄昏的亚灵长类哺乳动物有一个“本地”的组成部分，在孤立的括约肌，如两栖动物，鱼类和鸟类。在小鼠中，这种“局部”PLR需要最初在固有光敏视网膜神经节细胞（ipRGC）中发现的色素黑视蛋白。然而，黑视蛋白的存在和效应途径局部虹膜仍然不确定。括约肌本身可以表达黑视素，或者其胆碱能副交感神经支配可以通过所建议的行进到眼睛的睫状体或甚至虹膜的ipRGC的眼内轴突侧支来调节。在这里，我们表明，毒蕈碱受体拮抗剂，阿托品，消除了乙酰胆碱（ACh）的影响，但不是光，在离体小鼠括约肌。相反，选择性基因缺失的黑视蛋白在平滑肌主要消除光诱导的，但不是乙酰胆碱触发的增加孤立的括约肌的张力，并在很大程度上抑制了本地PLR在体内。因此，括约肌细胞是真正的光感受器，尽管是非常规的。我们发现黑视素表达在一小部分小鼠虹膜括约肌细胞中，光诱导的收缩信号明显通过缝隙连接扩散到邻近的肌肉细胞中。光和ACh在括约肌中共享共同的信号传导途径。总而言之，我们的实验提供了完全在视网膜外发生的眼睛光信号过程的细节。Wang等人表明，小鼠虹膜括约肌细胞的亚群表达视觉色素黑视蛋白，其光活化导致肌肉收缩和瞳孔收缩。因此，小鼠虹膜括约肌细胞是真正的，虽然非传统的，光感受器。
The mammalian pupillary light reflex (PLR) involves a bilateral brain circuit whereby afferent light signals in the optic nerve ultimately drive iris-sphincter-muscle contraction via excitatory cholinergic parasympathetic innervation. Additionally, the PLR in nocturnal and crepuscular sub-primate mammals has a “local” component in the isolated sphincter muscle, as in amphibians, fish and bird. In mouse, this ‘local’ PLR requires the pigment melanopsin originally found in intrinsically-photosensitive retinal ganglion cells (ipRGCs). However, melanopsin’s presence and effector pathway locally in the iris remain uncertain. The sphincter muscle itself may express melanopsin, or its cholinergic parasympathetic innervation may be modulated by suggested intraocular axonal collaterals of ipRGCs traveling to the eye’s ciliary body or even to the iris. Here, we show that the muscarinic receptor antagonist, atropine, eliminated the effect of acetylcholine (ACh), but not of light, on isolated mouse sphincter muscle. Conversely, selective genetic deletion of melanopsin in smooth muscle mostly removed the light-induced but not the ACh-triggered increase in isolated sphincter muscle’s tension, and largely suppressed the local PLR in vivo. Thus, sphincter muscle cells are bona fide, albeit unconventional, photoreceptors. We found melanopsin expression in a small subset of mouse iris sphincter muscle cells, with the light-induced contractile signal apparently spreading through gap junctions into neighboring muscle cells. Light and ACh share a common signaling pathway in sphincter muscle. In summary, our experiments have provided details of a photosignaling process in the eye occurring entirely outside the retina. Wang et al. show that a subset of mouse iris sphincter muscle cells express the visual pigment, melanopsin, with its photoactivation leading to muscle contraction and pupillary constriction. Thus, mouse iris sphincter muscle cells are bona fide, albeit unconventional, photoreceptors.
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