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Shannon Gallagher, Paul Witkovsky, Puneet Sodhi, Andrew Hartwick, Jozsef Vigh; µ-opioid receptor mediated modulation of ipRGCs. Invest. Ophthalmol. Vis. Sci. 2013;54(15):302.
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© ARVO (1962-2015); The Authors (2016-present)
Since their discovery, mechanisms for modulation of intrinsically photosensitive retinal ganglion cells (ipRGCs) have been elusive. Recently, we have identified the presence of the endogenous opioid system (β-endorphin and its preferred receptor) in the mammalian retina. In this study we investigated whether the ipRGCs are subject to opioid modulation.
Standard immunohistochemical procedures were utilized for melanopsin and µ-opioid receptor (MOR) colocalization experiments using rat retinas. Light-evoked spiking of ipRGCs was recorded from flat-mount retinas isolated from young (postnatal days 6-11) and adult (>3 months) Sprague Dawley rats of either sex using a 60 channel multielectrode array (MEA). Retinas were continuously superfused with oxygenated Ames medium at 37degC. Following dark adaptation, ipRGC spiking was recorded in response to 20 s light pulses (470nm; 7.5 x 10^14 photons x cm-2 x s-1). In all experiments, ipRGCs were pharmacologically isolated using a cocktail of synaptic blockers. The MOR selective agonist [D-Ala2, MePhe4, Gly-ol5]-enkephalin (DAMGO) was applied at various concentrations (1nM to 10 μM) for 10 min before light stimulation with/without MOR antagonist CTOP (1 to 10 μM).
Double labeling studies showed colocalization of MOR-ir puncta on the dendritic processes of melanopsin-ir cells in the rat retina. Consistent with this finding, DAMGO dramatically reduces the both the duration and firing rate of ipRGCs light responses in retinas from young (postnatal days 6-11) rats in a dose dependent manner. CTOP reversed the DAMGO effect. DAMGO affected ipRGCs similar in adult (>3months) retinas.
This is the first study to demonstrate that ipRGCs are subject to opioid mediated neuromodulation via µ-opioid receptors. Thus, retinal opioid signaling might influence light-dependent behavioral and/or disease processes in which involvement of ipRGCs is implicated.
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