Laboratoire des neurosciences de la vision, École d'optométrie, Université de Montréal, Québec, Canada.
Invest Ophthalmol Vis Sci. 2013 Dec 11;54(13):8079-90. doi: 10.1167/iovs.13-12514.
PURPOSE: Endocannabinoids are important modulators of synaptic transmission and plasticity throughout the central nervous system. The cannabinoid receptor type 1 (CB1R) is extensively expressed in the adult retina of rodents, while CB2R mRNA and protein expression have been only recently demonstrated in retinal tissue. The activation of cannabinoid receptors modulates neurotransmitter release from photoreceptors and could also affect bipolar cell synaptic release. However, the impact of CB1R and CB2R on the retinal function as a whole is currently unknown. METHODS: In the present study, we investigated the function of cannabinoid receptors in the retina by recording electroretinographic responses (ERGs) from mice lacking either CB1 or CB2 receptors (cnr1(-/-) and cnr2(-/-), respectively). We also documented the precise distribution of CB2R by immunohistochemistry. RESULTS: Our results showed that CB2R is localized in cone and rod photoreceptors, horizontal cells, some amacrine cells, and bipolar and ganglion cells. In scotopic conditions, the amplitudes of the a-wave of the ERG were increased in cnr2(-/-) mice, while they remained unchanged in cnr1(-/-) mice. The analysis of the velocity-time profile of the a-wave revealed that the increased amplitude was due to a slower deceleration rather than an increase in acceleration of the waveform. Under photopic conditions, b-wave amplitudes of cnr2(-/-) mice required more light adaptation time to reach stable values. No effects were observed in cnr1(-/-) mice. CONCLUSIONS: The data indicated that CB2R is likely to be involved in shaping retinal responses to light and suggest that CB1 and CB2 receptors could have different roles in visual processing.
目的:内源性大麻素是整个中枢神经系统中突触传递和可塑性的重要调节剂。大麻素受体 1(CB1R)在啮齿动物成年视网膜中广泛表达,而 CB2R mRNA 和蛋白表达最近才在视网膜组织中得到证实。大麻素受体的激活调节光感受器的神经递质释放,也可能影响双极细胞突触释放。然而,CB1R 和 CB2R 对整个视网膜功能的影响目前尚不清楚。
方法:在本研究中,我们通过记录缺乏 CB1 或 CB2 受体的小鼠(分别为 cnr1(-/-)和 cnr2(-/-))的视网膜电图反应(ERG)来研究大麻素受体在视网膜中的功能。我们还通过免疫组织化学记录了 CB2R 的精确分布。
结果:我们的结果表明,CB2R 定位于视锥和视杆光感受器、水平细胞、一些无长突细胞以及双极细胞和节细胞。在暗适应条件下,cnr2(-/-)小鼠的 ERG 的 a 波振幅增加,而 cnr1(-/-)小鼠的 a 波振幅则保持不变。对 a 波的速度-时间曲线进行分析表明,增加的振幅是由于波形减速而不是加速增加所致。在明适应条件下,cnr2(-/-)小鼠的 b 波振幅需要更多的光适应时间才能达到稳定值。在 cnr1(-/-)小鼠中未观察到影响。
结论:数据表明 CB2R 可能参与塑造视网膜对光的反应,并表明 CB1 和 CB2 受体在视觉处理中可能具有不同的作用。
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