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Mu-opioid system in the mammalian retina




Gallagher, Shannon K., author
Vigh, Jozsef, advisor
Clapp, Tod R., committee member
Gionfriddo, Juliet R., committee member
Hentges, Shane T., committee member
Partin, Kathryn M., committee member

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Until recently, the most solid evidence suggesting a role for endogenous opioids in mammalian visual processing has been the existence of μ-opioid receptors (MORs) in the retina. Nonetheless, in most reports the location of these receptors has been limited to retinal regions rather than specific cell-types. Reports on expression of endogenous opioids in the adult mammalian retina were missing, and even in juveniles have been sparse. Additionally, our knowledge of the possible physiological functions of opioid signaling in the retina is based on only a handful of studies using exogenous opioids. For example, the recent resurgence in retinal opioid research has focused on the somewhat controversial role of δ-opioid receptors in neuroprotection. The purpose of this work was to identify if the endogenous opioid peptide preferred by MORs, β-endorphin, is present in the mammalian retina, and to determine its possible influence on the light-evoked signaling of retinal neurons that express MORs. We have identified through use of transgenic mice, in situ hybridization and immunohistochemistry (IHC) that the cholinergic "Starburst" amacrine cells express β-endorphin. Using IHC we've shown that multiple neuronal cell types in the mouse retina possess MORs, including dopaminergic amacrine cells and intrinsically photosensitive retinal ganglion cells (ipRGCs). ipRGCs play a central role in mammalian non-image forming vision. Neuromodulatory processes that are capable of altering ipRGCs activity are likely to have profound consequences on light-mediated behavior and/or disease. Using IHC, we found that M1-M3 types of ipRGCs are MOR+ in both mouse and rat. Using electrophysiological techniques we found that DAMGO, a MOR selective agonist, dramatically reduces both duration and rate of light-evoked firing from rat and mouse ipRGCs. Our study is the first to demonstrate opioid modulation of light-evoked activity of neurons in mammalian retina. These findings demonstrate a new role for endogenous opioids in the mammalian retina and provide a novel site of action--MORs on ipRGCs--through which exogenous, systemically applied, opioids could exert an effect on light-mediated behaviors.


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intrinsically photosensitive retinal ganglion cells
multielectrode array


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