Delta-Opioid Agonist SNC-121 Protects Retinal Ganglion Cell Function in a Chronic Ocular Hypertensive Rat Model
Delta-Opioid Agonist SNC-121 Protects Retinal Ganglion Cell Function in a Chronic Ocular Hypertensive Rat Model
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DOI：
10.1167/iovs.12-10741
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发表时间：
2013-03-01
影响因子：
4.4
通讯作者：
Husain, Shahid
中科院分区：
文献类型：
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作者：
Abdul, Yasir;Akhter, Naseem;Husain, Shahid
目的。本研究探讨了 δ-阿片受体激动剂 SNC-121 是否可以改善慢性高眼压大鼠模型青光眼损伤期间的视网膜功能和视网膜神经节细胞 (RGC) 存活率。通过向角膜缘静脉系统注射高渗盐水来提高棕色挪威大鼠的眼压。大鼠接受 1 mg/kg SNC-121（腹膜内注射 [IP]）治疗，每天一次，持续 7 天。图案视网膜电图（PERG）是根据图案化视觉刺激的对比度反转而获得的。通过荧光金逆行标记使 RGC 可视化。通过免疫组织化学和蛋白质印迹法测量TNF-α和p38丝裂原激活蛋白(MAP)激酶的表达。结果。与健康眼睛（18.0 +/- 0.62 微伏）相比，高眼压眼的 PERG 振幅显着降低（14.3 +/- 0.60 微伏）。 SNC-121 治疗可抑制高血压眼的 PERG 损失（17.20 +/- 0.1.3 微伏；P < 0.05）。高眼压眼的 RGC 减少了 29%，而 SNC-121 的存在可以抑制这种损失。视网膜切片和视神经样本中 TNF-a 的产生和 p38 MAP 激酶的激活在高眼压眼中上调，但在 SNC-121 存在时受到抑制。此外，TNF-α 诱导的星形胶质细胞中 p38 MAP 激酶激活的增加在 SNC-121 存在下受到抑制。结论。这些数据提供证据表明，δ-阿片受体的激活抑制青光眼损伤期间 PERG 振幅的损失和 RGC 损失的速率。机制数据提供了线索，TNF-a 主要由神经胶质细胞产生并激活 p38 MAP 激酶，而 SNC-121 处理显着抑制该激酶。总体而言，数据表明，眼睛中δ-阿片能活性的增强可能会提供视网膜神经保护以预防青光眼。 （投资眼科可见科学。2013 年；54：1816-1828）DOI：10.1167/iovs.12-10741
PURPOSE. This study examined if the delta-opioid (delta-opioid) receptor agonist, SNC-121, can improve retinal function and retinal ganglion cell (RGC) survival during glaucomatous injury in a chronic ocular hypertensive rat model.METHODS. IOP was raised in brown Norway rats by injecting hypertonic saline into the limbal venous system. Rats were treated with 1 mg/kg SNC-121 (intraperitoneally [IP]) once daily for 7 days. Pattern-electroretinograms (PERGs) were obtained in response to contrast reversal of patterned visual stimuli. RGCs were visualized by fluorogold retrograde labeling. Expression of TNF-alpha and p38 mitogen-activated protein (MAP) kinase was measured by immunohistochemistry and Western blotting.RESULTS. PERG amplitudes in ocular hypertensive eyes were significantly reduced (14.3 +/- 0.60 mu volts) when compared with healthy eyes (18.0 +/- 0.62 mu volts). PERG loss in hypertensive eyes was inhibited by SNC-121 treatment (17.20 +/- 0.1.3 mu volts; P < 0.05). There was a 29% loss of RGCs in the ocular hypertensive eye, which was inhibited in the presence of SNC-121. TNF-a production and activation of p38 MAP kinase in retinal sections and optic nerve samples were upregulated in ocular hypertensive eyes and inhibited in the presence of SNC-121. Furthermore, TNF-a induced increase in p38 MAP kinase activation in astrocytes was inhibited in the presence of SNC-121.CONCLUSIONS. These data provide evidence that activation of delta-opioid receptors inhibited the loss of PERG amplitudes and rate of RGC loss during glaucomatous injury. Mechanistic data provided clues that TNF-a is mainly produced from glial cells and activates p38 MAP kinase, which was significantly inhibited by SNC-121 treatment. Overall, data indicate that enhancement of delta-opioidergic activity in the eye may provide retina neuroprotection against glaucoma. (Invest Ophthalmol Vis Sci. 2013;54:1816-1828) DOI:10.1167/iovs.12-10741