Department of Ocular Biology and Therapeutics, UCL-Institute of Ophthalmology, 11-43 Bath Street, London EC1V9EL, UK.
Department of Ocular Biology and Therapeutics, UCL-Institute of Ophthalmology, 11-43 Bath Street, London EC1V9EL, UK.
Exp Eye Res. 2014 Feb;119:8-18. doi: 10.1016/j.exer.2013.11.013. Epub 2013 Dec 5.
Maintenance of pupillary constriction in light-adapted rodents has traditionally been thought to involve a reflex between retina, brain and iris, with recent work identifying the melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) as the major conduits for retinal input to the brain. There is also a less well-understood phenomenon whereby the iris of some mammals, including mice, will constrict to light when either the eye, or the iris itself is physically isolated from the brain. The intrinsic pupillary light reflex (iPLR) is the term given to pupil constriction in the absence of retinal input to the brain. Here, using an intraocular axotomy approach, we show that the iPLR in conscious mice spans a dynamic range over 3 log units of irradiance. This iPLR response is absent in melanopsin knockout (MKO) mice and can be significantly inhibited by atropine. Immunohistochemistry for cfos and melanopsin, in combination with light exposure revealed a population of small ipRGCs in the retinal ciliary marginal zone (CMZ), which remain responsive to light in axotomised mice. We report that damage to the CMZ in a novel in vitro preparation removes a significant component of the iPLR response, while a detailed immunohistochemical analysis of the CMZ in wildtype mice revealed a melanopsin-rich plexus, which was consistently most intense in nasal retina. There were clear examples of melanopsin-positive, direct retino-ciliary projections, which appear to emanate from Brn3b negative, M1 type ipRGCs. These cells are clustered along the melanopsin-rich plexus nasally and may channel ipRGC signals from retina into the iris via ciliary body. Comparison between wildtype and MKO mice reveals that the ciliary body is also weakly stained for melanopsin. Our results show that the full extent of iPLR in mice requires cholinergic neurotransmission and intact signalling at the CMZ/ciliary body. This response may be mediated to some extent by ipRGCs, which send direct projections from the retina into ciliary body. In addition to the melanopsin-mediated iris sphincter constriction suggested by others, we propose a new mechanism, which may involve constriction of the ciliary body and ipRGC-mediated relaxation of the iris dilator muscle.
传统上认为，在光适应的啮齿动物中，瞳孔收缩的维持涉及视网膜、大脑和虹膜之间的反射，最近的研究确定表达黑视蛋白的固有光敏感视网膜神经节细胞(ipRGCs)是视网膜向大脑输入的主要途径。还有一种不太为人所知的现象，即包括老鼠在内的一些哺乳动物的虹膜在眼睛或虹膜本身与大脑物理隔离时，会对光收缩。内在瞳孔光反射(iPLR)是指大脑没有接收到视网膜输入时瞳孔收缩的术语。在这里，我们使用眼内轴突切断术方法，表明清醒小鼠的 iPLR 在辐照度超过 3 个对数单位的动态范围内。在黑视蛋白敲除(MKO)小鼠中，这种 iPLR 反应缺失，并且可以被阿托品显著抑制。cfos 和黑视蛋白的免疫组织化学，结合光暴露，揭示了视网膜睫状缘边缘区(CMZ)中一小群 ipRGCs 的存在，在轴突切断的小鼠中，它们对光仍然有反应。我们报告说，在一种新的体外制剂中，CMZ 的损伤消除了 iPLR 反应的一个重要组成部分，而对野生型小鼠 CMZ 的详细免疫组织化学分析显示，CMZ 中有一个富含黑视蛋白的丛，在鼻侧视网膜中始终最为强烈。有明确的黑视蛋白阳性、直接的视网膜-睫状突投射的例子，它们似乎来自 Brn3b 阴性、M1 型 ipRGCs。这些细胞沿着富含黑视蛋白的丛簇集，可能通过睫状体将 ipRGC 信号从视网膜传入虹膜。野生型和 MKO 小鼠之间的比较表明，睫状体也对黑视蛋白有微弱的染色。我们的结果表明，小鼠 iPLR 的全部范围需要胆碱能神经传递和 CMZ/睫状体的完整信号。这种反应可能在某种程度上由 ipRGCs 介导，它们从视网膜向睫状体直接投射。除了其他人提出的黑视蛋白介导的虹膜括约肌收缩外，我们还提出了一种新的机制，该机制可能涉及睫状体的收缩和 ipRGC 介导的虹膜扩张肌的松弛。
