• Allison M Cleymaet, Shannon K Gallagher, Ryan E Tooker, Mikhail Y Lipin, Jordan M Renna, Puneet Sodhi, Daniel Berg, Andrew T E Hartwick, David M Berson, and Jozsef Vigh.
• Dept. of Biomedical Sciences, Colorado State University, Ft. Collins, CO 80523; Dept. of Clinical Sciences, Colorado State University, Ft. Collins, CO 80523.
• Neuroscience. 2019 Jun 1; 408: 400417400-417.

AbstractIntrinsically photosensitive retinal ganglion cells (ipRGCs) encode light intensity and trigger reflexive responses to changes in environmental illumination. In addition to functioning as photoreceptors, ipRGCs are post-synaptic neurons in the inner retina, and there is increasing evidence that their output can be influenced by retinal neuromodulators. Here we show that opioids can modulate light-evoked ipRGC signaling, and we demonstrate that the M1, M2 and M3 types of ipRGCs are immunoreactive for μ-opioid receptors (MORs) in both mouse and rat. In the rat retina, application of the MOR-selective agonist DAMGO attenuated light-evoked firing ipRGCs in a dose-dependent manner (IC50 < 40 nM), and this effect was reversed or prevented by co-application of the MOR-selective antagonists CTOP or CTAP. Recordings from solitary ipRGCs, enzymatically dissociated from retinas obtained from melanopsin-driven fluorescent reporter mice, confirmed that DAMGO exerts its effect directly through MORs expressed by ipRGCs. Reduced ipRGC excitability occurred via modulation of voltage-gated potassium and calcium currents. These findings suggest a potential new role for endogenous opioids in the mammalian retina and identify a novel site of action-MORs on ipRGCs-through which opioids might exert effects on reflexive responses to environmental light.Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.

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