Laboratoire de Neuropharmacologie, École d'optométrie, Université de Montréal, Succursale Centre-Ville, C.P. 6128, Montréal, Québec, H3C 3J7, Canada.
Laboratoire des Neurosciences de la Vision, École d'optométrie, Université de Montréal, Montréal, Québec, Canada.
Sci Rep. 2020 Sep 25;10(1):15819. doi: 10.1038/s41598-020-72553-y.
Recently, there have been increasing indications that the endocannabinoid (eCB) system is involved in vision. Multiple research teams studied the cannabinoid receptor type 2 (CB2R) expression and function in the mouse retina. Here, we examined the consequence of CB2R modulation on visual acuity using genetic and pharmacologic tools. We found that Cnr2 knockout mice show an enhanced visual acuity, CB2R activation decreased visual acuity while CB2R blockade with the inverse agonist AM630 increased it. The inhibition of 2-arachidonylglycerol (2-AG) synthesis and degradation also greatly increased and decreased visual acuity, respectively. No differences were seen when the cannabinoid receptor type 1 (CB1R) was deleted, blocked or activated implying that CB2R exclusively mediates cannabinoid modulation of the visual acuity. We also investigated the role of cannabinoids in retinal function using electroretinography (ERG). We found that modulating 2-AG levels affected many ERG components, such as the a-wave and oscillatory potentials (OPs), suggesting an impact on cones and amacrine cells. Taken together, these results reveal that CB2R modulates visual acuity and that eCBs such as 2-AG can modulate both visual acuity and retinal sensitivity. Finally, these findings establish that CB2R is present in visual areas and regulates vision-related functions.
最近,越来越多的迹象表明内源性大麻素(eCB)系统参与视觉过程。多个研究小组研究了大麻素受体 2 型(CB2R)在小鼠视网膜中的表达和功能。在这里,我们使用遗传和药理学工具研究了 CB2R 调节对视敏度的影响。我们发现,Cnr2 基因敲除小鼠表现出增强的视觉敏锐度,CB2R 的激活降低了视觉敏锐度,而反向激动剂 AM630 阻断 CB2R 则增加了视觉敏锐度。2-花生四烯酸甘油(2-AG)合成和降解的抑制分别极大地增加和降低了视觉敏锐度。当删除、阻断或激活大麻素受体 1(CB1R)时没有看到差异,这表明 CB2R 专门介导大麻素对视觉敏锐度的调节。我们还使用视网膜电图(ERG)研究了大麻素在视网膜功能中的作用。我们发现调节 2-AG 水平会影响许多 ERG 成分,例如 a 波和振荡电位(OPs),这表明对锥体和无长突细胞有影响。综上所述,这些结果表明 CB2R 调节视觉敏锐度,而 2-AG 等 eCB 可以调节视觉敏锐度和视网膜敏感性。最后,这些发现表明 CB2R 存在于视觉区域并调节与视觉相关的功能。