Someya Eriko, Mori Asami, Asano Daiki, Morita Akane, Sakamoto Kenji, Nakahara Tsutomu
a Department of Molecular Pharmacology , Kitasato University School of Pharmaceutical Sciences , Tokyo Japan.
Curr Eye Res. 2018 Mar;43(3):350-356. doi: 10.1080/02713683.2017.1403631. Epub 2017 Nov 27.
Our recent study demonstrated that herkinorin, a non-opioid μ-receptor agonist derived from salvinorin A, dilates retinal arterioles through stimulation of μ-opioid receptors in rats. Activation of neuronal nitric oxide (NO) synthase and the presence of ganglion cells in the retina appear to be crucial for inducing μ-opioid receptor-mediated retinal vasodilation. In the present study, we examined the role of the interaction between neurons and glia in the retinal vasodilator mechanism involving μ-opioid receptors in rats.
The localization of μ-opioid receptors and neuronal NO synthase (nNOS) in the rat retina was examined using immunohistochemistry. The retinal vascular responses were evaluated by measuring the diameter of retinal arterioles in in vivo fundus images. Both systemic blood pressure and heart rate were continuously recorded.
Immunoreactivity of μ-opioid receptors was found in ganglion cells and astrocytes, while that of nNOS was detected in ganglion cells and amacrine cells. Herkinorin increased retinal arteriolar diameter without significantly changing mean blood pressure and heart rate. The retinal vasodilator response to herkinorin was significantly attenuated by treatment with glial toxins (fluorocitrate and disialoganglioside-GD1b). The glial toxins markedly prevented vasodilation induced by intravitreal injection, but not by intravenous infusion, of NOR3, an NO donor.
These results suggest that retinal glial cells play an important role in the μ-opioid receptor-mediated retinal vasodilation in rats. Stimulation of μ-opioid receptors on retinal ganglion cells may affect the activity of glial cells, thereby changing retinal vascular tone.
我们最近的研究表明，herkinorin是一种从Salvinorin A衍生而来的非阿片类μ受体激动剂，它通过刺激大鼠的μ阿片受体使视网膜小动脉扩张。神经元型一氧化氮（NO）合酶的激活以及视网膜中神经节细胞的存在似乎对诱导μ阿片受体介导的视网膜血管舒张至关重要。在本研究中，我们研究了大鼠视网膜血管舒张机制中神经元与神经胶质细胞之间相互作用的作用，该机制涉及μ阿片受体。
使用免疫组织化学检查大鼠视网膜中μ阿片受体和神经元型NO合酶（nNOS）的定位。通过测量体内眼底图像中视网膜小动脉的直径来评估视网膜血管反应。连续记录全身血压和心率。
在神经节细胞和星形胶质细胞中发现了μ阿片受体的免疫反应性，而在神经节细胞和无长突细胞中检测到了nNOS的免疫反应性。Herkinorin增加了视网膜小动脉直径，而没有显著改变平均血压和心率。用神经胶质毒素（氟柠檬酸和二唾液酸神经节苷脂-GD1b）处理后，herkinorin引起的视网膜血管舒张反应明显减弱。神经胶质毒素显著阻止了玻璃体内注射NO供体NOR3诱导的血管舒张，但对静脉输注NOR3诱导的血管舒张没有影响。
这些结果表明，视网膜神经胶质细胞在大鼠μ阿片受体介导的视网膜血管舒张中起重要作用。刺激视网膜神经节细胞上的μ阿片受体可能会影响神经胶质细胞的活性，从而改变视网膜血管张力。
