Endogenous Opioid Signaling in the Mouse Retina Modulates Pupillary Light Reflex.
Endogenous Opioid Signaling in the Mouse Retina Modulates Pupillary Light Reflex.
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DOI：
10.3390/ijms22020554
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发表时间：
2021-01-08
影响因子：
5.6
通讯作者：
Vigh J
中科院分区：
文献类型：
--
作者：
Cleymaet AM;Berezin CT;Vigh J
阿片肽及其受体在哺乳动物的视网膜中表达；然而，人们对它们如何影响视觉处理知之甚少。表达黑素的固有光敏性视网膜神经节细胞(IpRGC)介导重要的非成像视觉过程，如瞳孔光反射(Plr)，表达β-内啡肽偏好、µ-阿片受体(MORs)。本研究的目的是阐明内源性或外源性阿片类物质是否通过ipRGC表达的MORS来调节瞳孔光反射(PLR)。玻璃体腔注射MOR选择性激动剂[D-Ala2，MePhe4，Gly-ol5]-脑啡肽(DAMGO)或拮抗剂D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2(CTAP)。记录PLR对不同强度光刺激的反应。DAMGO消除了由低于黑素激活阈值的光引起的PLR，但不能消除由激活黑素信号的明亮蓝色辐射引起的PLR，尽管在后一种情况下，DAMGO显著减缓了瞳孔收缩。CTAP或MORS基因消融后，ipRGC的弱光诱发的PLR略有增加，但亮蓝色刺激诱发的PLR不明显。我们的结果表明，视网膜内的内源性阿片信号参与了PLR的调节。DAMGO对强光诱发的PLR的减缓与系统应用阿片类药物在玻璃体中积聚以及接受长期阿片类药物治疗的患者PLR缓慢的观察结果一致。
Opioid peptides and their receptors are expressed in the mammalian retina; however, little is known about how they might affect visual processing. The melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs), which mediate important non-image-forming visual processes such as the pupillary light reflex (PLR), express β-endorphin-preferring, µ-opioid receptors (MORs). The objective of the present study was to elucidate if opioids, endogenous or exogenous, modulate pupillary light reflex (PLR) via MORs expressed by ipRGCs. MOR-selective agonist [D-Ala2, MePhe4, Gly-ol5]-enkephalin (DAMGO) or antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) was administered via intravitreal injection. PLR was recorded in response to light stimuli of various intensities. DAMGO eliminated PLR evoked by light with intensities below melanopsin activation threshold but not that evoked by bright blue irradiance that activated melanopsin signaling, although in the latter case, DAMGO markedly slowed pupil constriction. CTAP or genetic ablation of MORs in ipRGCs slightly enhanced dim-light-evoked PLR but not that evoked by a bright blue stimulus. Our results suggest that endogenous opioid signaling in the retina contributes to the regulation of PLR. The slowing of bright light-evoked PLR by DAMGO is consistent with the observation that systemically applied opioids accumulate in the vitreous and that patients receiving chronic opioid treatment have slow PLR.
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影响因子：
14.8
作者：
Jones, Kenneth A.;Hatori, Megumi;Mure, Ludovic S.;Bramley, Jayne R.;Artymyshyn, Roman;Hong, Sang-Phyo;Marzabadi, Mohammad;Zhong, Huailing;Sprouse, Jeffrey;Zhu, Quansheng;Hartwick, Andrew T. E.;Sollars, Patricia J.;Pickard, Gary E.;Panda, Satchidananda
通讯作者：
Panda, Satchidananda
影响因子：
64.8
作者：
Do, Michael Tri H.;Kang, Shin H.;Xue, Tian;Zhong, Haining;Liao, Hsi-Wen;Bergles, Dwight E.;Yau, King-Wai
通讯作者：
Yau, King-Wai
影响因子：
1.9
作者：
Gallagher, Shannon K.;Anglen, Julia N.;Mower, Justin M.;Vigh, Jozsef
通讯作者：
Vigh, Jozsef
影响因子：
4.4
作者：
Cadet, P;Mantione, KJ;Stefano, GB
通讯作者：
Stefano, GB
影响因子：
64.8
作者：
Gueler, Ali D.;Ecker, Jennifer L.;Hattar, Samer
通讯作者：
Hattar, Samer