Department of Biomedical Sciences, Colorado State University, Ft. Collins, CO 80523, USA.
Department of Clinical Sciences, Colorado State University, Ft. Collins, CO 80523, USA.
Int J Mol Sci. 2021 Jan 8;22(2):554. doi: 10.3390/ijms22020554.
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-Ala, MePhe, Gly-ol]-enkephalin (DAMGO) or antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH (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.
阿片肽及其受体存在于哺乳动物视网膜中；然而，关于它们如何影响视觉处理，目前知之甚少。表达黑视蛋白的光感受器神经节细胞(ipRGCs)介导重要的非成像视觉过程，如瞳孔光反射(PLR)，表达β-内啡肽优先、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 ipRGCs 表达的 MOR 来调节瞳孔光反射(PLR)。通过玻璃体内注射给予 MOR 选择性激动剂[D-Ala，MePhe，Gly-ol]-脑啡肽(DAMGO)或拮抗剂 D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH(CTAP)。记录对不同强度光刺激的 PLR。DAMGO 消除了低于黑视蛋白激活阈值的光诱发的 PLR，但不能消除激活黑视蛋白信号的亮蓝光诱发的 PLR，尽管在后一种情况下，DAMGO 明显减缓瞳孔收缩。CTAP 或 MOR 在 ipRGCs 中的基因缺失略微增强了弱光诱发的 PLR，但不能增强亮蓝光刺激诱发的 PLR。我们的结果表明，视网膜内源性阿片信号参与了 PLR 的调节。DAMGO 对强光诱发的 PLR 的减缓与以下观察结果一致，即系统应用的阿片类药物在玻璃体内积聚，以及接受慢性阿片类药物治疗的患者的 PLR 缓慢。
