Endogenous Opioid Signaling in the Mouse Retina Modulates Pupillary Light Reflex.

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 ß-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.

Unfolding the diagnosis of subspectacular fluid opacity in a corn snake (Pantherophis guttatus).

OBJECTIVE: To present the results of clinical, surgical, and histopathologic procedures and how these were compared with the initial presumptive clinical diagnosis in a corn snake (Pantherophis guttatus) presenting with subspectacular fluid opacity; and to improve upon currently established surgical enucleation techniques in the snake. ANIMAL STUDIED: An 8-month-old corn snake was presented for enlarged globe OD. PROCEDURES: The following diagnostics were performed: systemic and ophthalmic examinations, complete blood count, cytology and culture of subspectacular fluid, and histopathology of enucleated globe and spectacle. Enucleation was performed in a routine fashion with the addition of a porcine small intestinal submucosa bioscaffold graft (SISplus™; Avalon Medical, Stillwater, MN), sutured over the orbit. RESULTS: Systemic examination revealed signs of maxillary stomatitis. Ophthalmic examination revealed semitransparent fluid in the subspectacular space. Complete blood count was unremarkable. Cytology of fluid obtained via subspectacular centesis was acellular, and culture grew Clostridium perfringens, which was consistent with the clinical suspicion of right maxillary stomatitis. Histopathology of the enucleated globe revealed spectaculitis, characterized by regional heterophilic inflammation, and no evidence of lymph dissection in the (peri)ocular tissues. The final diagnosis was a subspectacular abscess. Follow-up revealed that the SIS graft provided excellent healing and cosmesis of the surgical site. CONCLUSIONS: While there are reports of lymphatic fluid dissection between skin layers during ecdysis, which can result in an opaque spectacle, the fluid opacity in this case was attributed to a subspectacular abscess secondary to an ascending oral infection. Addition of biological wound dressing may contribute to positive post-enucleation outcome in the snake.

µ-Opioid Receptor Activation Directly Modulates Intrinsically Photosensitive Retinal Ganglion Cells.

Intrinsically 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.